Some Possible Anti-viral Drugs for COVID-19 :

POLY-ANIONIC HEPARIN LIKE

COMPOUNDS --
POLYINORGANIC PHOSPHATEs
Also gases.
By D Grant (PhD in Chemistry) Turriff AB53 UK

Take not however

N.b. THIS IS NOT MEDICAL ADVICE

However May Help Curb Pandemics

This is a quick journey for through the net randomly accessing sites which may offer new information possibly leading
eventually to improved public health and ways of combatting COVID-19.

Contents. 1. Preamble. Gases Impact on Viral Infection Through the Transport of Viruses in Aerosols

1-1 CONCEPT : Vaping for (straight drug use) -killing for COVID-19

2. CONCEPT OF GAS/VAPOUR use to kill COVID-19 in airways and lungs

2-1. Vapours for (straight drug use) -killing for COVID-19

3. Stopping viral induced cough or sneeze

4. More on Antiviral gases very dilute highly toxic CHLORINE DIOXIDE (ClO2)

4-a. Supply of face masks

4-1. PERCHLORATE (Part on anthropogenic from ozonisation of chloride).Thyroid pituitary axis & viruses

4-1-1. potassium IODIDE is an established drug to counter respiratory viruses

4-2. Smokers have corelated cigarette number with thiocyanate -> hypothiocyanous acid which monomerizes eNOS

and creates an associated decrease in NO. This action has both positive and negative effects on viruses.

5. The urban air nitrogen dioxide (NO2) levels are apparently associated with human virus loads

6. HYDROGEN (H2) THERAPY for COVID-19

7. INORGANIC PRO- and ANTI-VIRAL GAS Balancing Act. The latter can be administered as solid precursors.

NO (NITRIC OXIDE(a gas-o-transmitter) which together with H2S and CO is an antiviral system but also shows high pro-RNA
viral mutation activity.

7-1 NOVEL HYDROGEN SULPHIDE (ex slow-release H2S DONOR) THERAPY FOR PNEUMONIA

7-2. Benzothiazoles

7-3. Dimethyl Sulphide Scotch whiskey and wine oak barrel aged

8. MORE ON: Nasal Aerosol Delivery of Antiviral Drugs

9. FOOTNOTES Need more research into listed topics

9-a. CONVENTIONAL ANTIVIRAL DRUGS & COVID-19

9-1. SALT WATER (aerosol?) a simple antiviral THERAPY

9-1-1. Ammonium Chloride

9-1-2. PAW water

9-2. 10 Convalescent Plasma

Seems to be a little like milk for its immune protection

10-1. SO, DOES MILK (human from exposed populations but perhaps also from other species exposed toCOVID 19) protect
against COVID-19? (Cf. “Health experts debunk claim about milk and COVID-19 Sky News” Given fake information tag by
Facebook.

11. Mannose Binding Lectin (MBL)

11-1. Banana lectin

12. More Inorganic-chemistry-related antivirals

13. The Linus Pauling anti-common cold high ascorbate hypothesis.

14. Why do agents which may have beneficial effect in Alzheimer’s disease also possibly inhibit coronavirus infections?

15. SULFONAMIDE antivirals

16. INORGANIC POLYMERS AS ANTIVIRALs

POLY-INORGANIC-PHOSPHATE.

Also poly Phosphonates & Related

16-1. Could Silicon Biochemicals Act as Pro-Viral or could these also Help Fight Viruses? Or are SiO 2 nanoparticles so similar to viruses that
they could easily become virus promoters

16-1-1. HINT OF A NEW HYPOTHESIS: Amorphous SILICA nanoparticles synergise with viruses including those in the gut to enhance viral
infection of the lungs

16-2. more on POLY-INORGANIC-PHOSPHATE later insertion PolyPis seems a Potential COVID-19

Antiviral System.
A KEY easily produced antiviral system is IDENTIFIED for possible quick combat against
COVID-19
17. Heparin-like Polyanion Broad-Spectrum Antivirals & Related.

18. Anti-malaria drugs for anti COVID-19 therapy

18-1. Serotonin reuptake inhibitors (but not Statins) show anti-HIV antiviral activity in vivo

19. Other Antivirals

20. MISC. Cystic fibrosis technique

1. Preamble
The human population of the Earth now needs a
proper anti-viral strategy conceived to stop gas phase
transfer of viruses as well as direct person to person
transfer of viruses. Also new antiviral broad spectrum
drugs including those which release H2S in vivo.
Silica nanoparticles may exacerbate viral damage to
the lungs both directly and via gut-lung axis. Silica nanoparticles occur
in the air (and may bind to viruses and increase virulence); an additional enhancement of viruses utativley arises from interactions in the
gut with silica nanoparticles used as food additives.

The smallest size aerosols emitted from virus

carriers travel furthest in the air including
attached to (e.g. bound to dust SiO2 nanoparticles).
Need to think how to properly sterilize urban air.
Already do this for urban water. Need to think
big. (Future cities: massive air-conditioned big-
bubble? Or sub-bubbles; both with large-scale air-
conditioning).

Simple gases (e.g. NO2 and CO) which are increased in

urban areas can impair human health by making urban
residents more prone to viral infections. The larger the
city the greater is the hazard. Need to find out how to
re-create cities that work better.
Sulphuric acid and related aerosols from fossil fuel
combustion seems like bad news but changeover from
S-rich fuels caused S-depletion in soils worldwide
which transfers on to sulphated human molecule
endogenous antiviral depletion. The recent exponential
growth of literature describing how H2S signalling
controls much of biochemistry allows intervention by
drugs which seek to control this.
Some gases (this includes man-made ‘vapours’ of
essential oils) have directly beneficial therapeutic
antiviral properties perhaps via the H2S system. These
might be critically useful under present day conditions.

2.
CONCEPT OF GAS/VAPOUR: the correct balance is
needed to kill COVID-19 in the airways and lungs.
Chloroform (CHCl3) containing lozenges (formerly
available over the counter) were traditionally
used to combat winter flu. Probably via solvent
dissolution of viral oily coat. Also similar menthol
use.
The targeting of the hydrophobic viral coat is what
hand washing is believed to accomplish.
Better to get into the airways however.
This suggests a modern equivalent: menthol e-
cigarettes especially using e.g. Sage-derived
Essential Oils which have shown antiviral including
anti-SARS-CoV properties (cf. PMID 31195752).
For other essential oils with antiviral properties
see PMID 31195752.
[Cf. Sage anti—coronavirus (e.g. via camphor and
1-8-cineol). Eucalyptus is anti influenza H1N1;Tea
tree is a anti HSV-1)].

2-1.
Simple ways (to do straight drug use) viral killing:
COVID-19.
Other traditional gas methods used: burning of cinnamon. Did tobacco burning products
have antiviral properties?
Sniff snuff (?) [non-academic web reports].
Sniff essential oils. Like aromatherapy.
More drastic: burning of yellow sulphur .
Might design a tobacco with added very low sulphur content.
Or a vaping fluid containing the range of disinfectant substances listed as being antiviral
which includes alcohols etc.
Might improve on this using essential oils.
Can use essential oil candles.
or more invasive handwashing e.g. using sulphur soaps.

Can use nitric oxide, hydrogen sulphide or

hydrogen to combat viruses.
Can also use
Ozone (O3) therapy for complex regional pain.
PMID 31062104.
Can use O3 generators in rooms to combat
airborne viruses.

3. Getting back to basics

A prime logical human-society threat event is the gas borne particles induced
COVID-19 infection is

viral induced cough or sneeze. To block the primary viral human

population infection process we logically need to prevent the sneezing/cough event in the first
place.

Cf. AH Morice Clin Pharmacist 2017 Mar. Cough reflex hypersensitivity induced by a virus is a (can
fundamental phase of upper respiratory tract infection (insert text ‘and further infection of lun’g).
The pandemic virus is spread by coughing. Such viruses are good at inducing such coughing.
Treatments exist but usually at the over the counter drug level. This needs to be updated.

S1-1 Smallest aerosols carrying COVID 19 likely to go far, being airborne suggests selective
mandatory advice (or directive) requiring general use of drugs to inhibit
public space cough/ sneeze.
Possible but controversial use of very low concentrations of virus-bearing ultr-nanoparticles.

4.
More on Antiviral Gases
Very dilute highly toxic ClO2
Can choose to ignore US Govt advice and use

CHLORINE DIOXIDE (ClO2) gas to sterilize public space air and

surfaces? (Cf. PMID 18089729; 21950421; 27041456).

N.B. An April 08 press release from the US FDA however warned the public against using to combat
COVID-19 (Claiming vendors were engaged in fraudulent activity).

Use of (aerosol)) sodium chloride (NaCl) solution to combat influenza viruses was however supported by an Edinburgh
university clinical trial ELVIS) where the antiviral effect was believed to be dependent on generation of hypochlorous and
possibly ultra-trace chlorine radical and chlorine dioxide in the nose and throat. (PMID 30705369).

This academic study suggests use of ‘activated chlorine’ including ClO 2 against all viruses.

Chloroquine and other chlorinated organics may however generate ultralow Cl. and ClO2 in vivo. (Hypochlorous acid is uses by activated
phagocytes to kill pathogens; cf.

Chloroform (CHCL3)lozenges (discussed above) were widely used many

years ago to combat influenza..

Some marine fungal antibiotics (PMID 14632284) contain organochlorine moieties. Also, note that:

MANY LONG-IN-USE DISINFECTANT FORMULATIONS CONTAIN ORGANOCHLORINE MOLEUCULES INCLUDING CHL0RINATED

PHENOLS.

See the list of such molecules in PMID 9880479.

Butylperchlorocrotonate is used industrially to generate low levels of chlorine radicals to re-oxidize deactivated transition metal catalysts
albeit used in an anaerobic environment. Other chlorinated organics do likewise but less efficiently. These catalyst promoters include

CHCl3 and chlorinated aromatics (cf. WO200000517A!) suggesting a similar mechanism may underpin antimicrobial including antiviral
activities of all chlorinated organic molecules used as antiseptics.
4-a. Supply of face masks
If (as happens with smallest aerosols) COVID-19 virus is airborne, the public
needs a supply of masks for all and should also think about how to sterilize
public air especially in and around hospitals (esp. for future pandemics).

Some think public air in most cities is OK for COVID-19, so masks are unnecessary. Information is
currently insufficient however. Cf. E Yong, The Atlantic April 1 2020 “Is the Coronavirus Airborne?
Should We All Wear Masks”.

Urban air may contain pro-virus factors. These may be correlated to Car Exhaust Nitrogen Oxides.
(The orange-brown colour seen over cities). {Satellite images show decreases during lockdown).

4-1.
Chlorate ClO3-
Cf series of Cl oxide/oxyacids
OCl3- + OCl- ↔→ ClO4- + Cl-

2 OCl- ↔→ ClO2 + Cl-

from chlorite to
PERCHLORATE (ClO4-) which occurs globally in
air and water (also in food and milk) (part only
anthropogenic from ozonization of chloride also
urban enhancement hence of interest for
explaining pandemics). Thyroid pituitary axis &
also affects viruses via →major effect of
CHLORATE : Inhibition of enzymatic HEPARAN
SULPHATE SULPHATION (PMID 10593915)
hence decreases this GAG-afforded major innate
cell surface antiviral defence.
Removal of perchlorate in water and air is needed
to decrease viral epidemics.
Is perchlorate also correlated with nitrogen
dioxide?
Cf. titration of nitrogen dioxide with perchlorate.

Cf. virucidal efficacy of inorganic per-compounds

Perchlorate and permanganate (which is especially
effective) (PMID 1652966).

4-1-1. KI (potassium IODIDE) (e.g. oral 130mg) counters

respiratory virus infections. Cf. PMID 21441383.

Needs to get tested for COVID-19.

4-2. Smokers have correlated cigarette number with airway thiocyanate →

hypothiocyanous acid (HOSCN) which deactivates (monomerizes) eNOS causing NO gas
diminution (PMID 24112082) tending to increase oxidative stress but may additionally via
altered other enzyme activity be indirectly antiviral via bacteria reduction (PMID 23629660)
putatively induced mucus viscosity reduction. This means some effects of tobacco smoking
may be unexpectedly beneficial during a viral pandemic. It’s a balance of major pro-cancer

harm and possible antimicrobial benefit .

 5.
Urban air nitrogen dioxide (NO2) gas levels
are apparently directly associated with an
increased human virus load and resultant
epidemics in urban populations. There is therefore for a
more effective antiviral environment to aid therapy, an obvious pressing need to remove NO 2 from
urban air. The use of NO2 absorbers (e.g. tin disulphide cf. Jen Ou J ACS Nano Oct 28 2015 RMIT U) is
of interest including for personal mask air intake protection.

On the other hand, If urban air is often OK this could indicate that some air pollutants are killing the
viruses.

This could be benzothiazoles present in high tonnage from tyre tread wear input into air

Also Ozone (O3). (Cf. suggested use for killing viruses by apheresis).

Also dioxins and related substances. These are, however also thought to diminish human immune
system responses to virus infections. There seems to be correlation between type 2 diabetes and
organochlorine intoxication levels. Obviously partly diet-induced.

Organochlorines are self-assembled during normal combustion processes where chlorine types (e.g.
Cl- ion) occurs in the air. E.g. hexachlorobenzene, hexachloroethane and carbon tetrachloride are
formed from any chlorocarbon heat induced randomization or from incineration of
polyvinylchloride.

This organochlorine intoxication cocktail leads on to decreased natural killer cell efficiency.

6.
HYDROGEN (H2)THERAPY for COVID-19
infection?
Info obt. via Web search term “hydrogen gas therapy coronavirus” ->

“Hydrogen gas therapy for COVID-19 acute respiratory distress syndrome (ARD) in
Medium (document by Vaibhav Mar 21 2020).
H2 (gas therapy) might especially benefit the subset of hyper inflammation (cytokine
storm) ARD patients.
Zhong Nashan (discoverer of the SARS coronavirus) is believed to have used O 2-H2 gas
inhalation for SARS therapy.
Duried Alwazeer (Researchgate) document ‘Potential Cheap and Effective Drugs’ for COVID-19 #.

Cf. also PMC 5964155; Ohsawa T et al. Nat Med 2007 13 (6) 681-94.

H2 therapy: counters peroxynitrite. H2 is a powerful antioxidant. Cf.

Pathogensis of influenza virus induced pneumonia … Akaike T et al PNAS 1996 93(6) 2448-
53; IFNγ -> iNOS -> NO excess causing tyrosine nitration (indication of excess inflammation
via peroxynitrite which however can be neutralized by exogenous H2; cf. ‘Hydrogen gas in
cancer treatment’ Li S et al. Front Oncol 06 Aug 2019.
Q and ans. Discussion info from WY Wu Toronto 3rd May 2020: Qui P et al Nat Med 2007
13 688-96; Int J Biol Sci 2019 15(6) 1261-75 PMID 17486089.

7.
INORGANIC PRO- and ANTI-VIRAL GAS Balancing
Acts
Removing air-borne oxidant gases induced human
intoxication by
administration of H2S-generatinf solid precursor
drugs.
NO
 NITRIC OXIDE (a gasotransmitter with H S and CO) & 2

antiviral but also shows high pro-RNA viral

mutation activity.
The anti-Coronavirus COVI-19 activity
of NO needs looking at.
As does the pro-RNA virus effect of NO2
NITROGEN DIOXIDE
COFACTOR (together with O ) in the aetiology of
3

VIRAL PNEUMONIA (cf. C Pirozzi CS et al. Ann Am Thoracic Soc 2018 15 (4) 449-59

While high NO2 air contents have associated with mini epidemics of acute
respiratory illnesses in ice rinks (PMID 11741827) suggesting that

COVID-19 infection rates may greater in

those cities with higher urban air NO2 and O.
levels On the other hand

NITRIC OXIDE (NO), has long been known

to be involved in combatting virus
infections (cf. PMID 11106932); nitric
oxide synthase (iNO) is ubiquitously
expressed in response to virus infections,
but a common problem with NO which
had seemed to downgrade its possible
therapeutic use for antiviral therapy was
 that the NO which gets overexpressed
under microbial infection conditions also
causes unacceptable tissue damage (e.g.
via NO metabolites nitrite, nitrous acid
and peroxynitrite).
{E.g. a hypothesis of the origin of degenerative diseases and chronic fatigue syndrome posited that
defects in NO facilitated heparan sulphate scission were central to these conditions Aberdeen U FB

Williamson pers. disc. }

THE NEW KID ON THE BLOCK HYDROGEN SULPHIDE put. Involved w Golgi
stabilization but also as a nitric oxide toxicity controller, completely alters
this .

In recent years a entirely new insight has

been achieved into NO biochemistry:

HYDROGEN SULPHIDE H 2S (
->polysulphides) and more generally redox status
Dramatically influences NO status;
There is a critical NO-H2S-CO crosstalk
system in biota (cf.
Cortese-Krott MM, PNAS 2015 112 E4651-
60; PMID 26224837). Other research
groups (e.g. Aberdeen) had also
considered that under adequate
ascorbate status conditions the
formation of excessive NO metabolites
are kept under control. Excessive
uncontrolled NO causes cancer and other
diseases. This concept needs to be
addressed if exogenous NO or NO-
releasing agents are to be successful used
to combat viruses. The related H S presence can be seems to be
2

an essential part of the successful antiviral activity of NO. This means that
commonly found defective ascorbate dietary intake or H2S status means that while
NO is antiviral per se it also causes pro-disease and tissue damaging side effects if
the redox system is out of balance.

The RATE OF RNA VIRAL EVOLUTION is

believed to be dependent upon NO-
induced mutation. This creates drug-
resistant strains. New strains are easily
formed. Cf. PMID 15280479.
RNA viruses undergo fast nucleic acid
mutation. It is, however, likely that H2S is
also involved here..
 dependent on NO-H2S-Polysulphide
biochemistry.
May also crosstalk with other systems e.g. glycosaminoglycans and polyinorganic phosphates.

Nitric Oxide INHIBITS a CORONOVIRUS *KEY Ref PMID 15234326

Potentially directly as well as via a library of antiviral sulphated oligosaccharides etc. generation

A large variety of (pharmaceutical)

Nitric Oxide (NO) donors

are currently available for testing against COVID-19 infection.
NO metabolites cause heparan scission -> potential antiviral oligosaccharides

especially under acute phase conditions with Cu elevation.

Putatively also hydrogen sulphide (H2S )-related protein (sulhhydration and polysuphides) could be
involved here.

Cf. NO donor S-nitroso-NAc penicillamine inhibits

SARS-COV V concentration dependently (Akerström et
al. PMID 15650225 cf. 19800091).
Again restating a key situation: NO works under
hydrogen sulphide (H2S) control
(Insert H2S per se is also a likely potent antiviral
Cf. H2S ex GYY4137 combats respiratory syncytial virus airway infection PMID 27314446; cf. also Bazhanov N et
al. SciRep 7 Art No. 41029(2017);

(N.b. H2S is active against H1N1 influenza virus).

Related? antiviral H2O2/ catalase 32107411;

Antiviral activity of H2S, cf. PMID 25740991).

7-1.
NOVEL HYDROGEN SULPHIDE (ex slow release H2S
DONOR) THERAPY FOR PNEUMONIA
Although the following paper reported on respiratory syncytial virus (RSV) the findings may be of
more general relevance (cf. Bazhanov N, SciRep 2017 7 41029 and may also apply to COVID-19.

Does the H2S in mineral (spa) water also combat viral

infections of the airways?
Cf. sulphurous mineral water has been found to be of
benefit for airway infections for centuries and is
reported to inhibit chronic obstructive pulmonary
disease (COPD) etc.
(Cf. sites accessed from web survey term “H2S spring
water antiviral”:-
Carbajo JM & Maraver F PMID 28484507 and also later
paper by Viegas J et al. f.pubh.2019.00128.
H2S in the correct concentration can be anti-pathogen
including anti-viral (cf. e.g. PMID 19659653) but there
is some confusion of the exact situation.

7-2.
Benzothiazoles.
58 compounds of this class studied most inactive 5
were of moderate antiviral activity.
Needs re-appraisal. Cf.
Vulcanized tyre rubber airborne nanoparticles.
(Does this bind viruses? Maybe neutralizes them?
It is of some interest, but scarcely thought elsewhere to merit comment in the public health
scenario, that a gigantic environmental input into the air consists of vulcanized tyre rubber
nanoparticles which retain large tonnage benzothiazole disulphide vulcanization accelerator [Large tonnage road
xenobiotic: tyre-wear-generated rubber nanoparticle

B -S-S-B where B is benzothiazole

aerosols containing this are likely to impact on viral infection.

The popular vulcanization accelerator

2,2'-dithiobisbenzothiazole (can target H2S redox

system] seems chemically constituted to

allow a pro-health slow H2S release in vivo including in the airways and lungs and if this hypothesis is correct
such pollution may counter the damage to lung tissues caused by cigarette smoke and other urban air
particulates which putatively are positively correlated with deaths from viral infections causing pneumonia.

Cf. H2S (Hydrogen Sulphide May be Promising Tool to Fight Highly Infectious Viruses, Antonella Casela UTMB
Texas Medical Center June 25 2017). Cf. also T Ivanciuc 2016 and J Viego 2019; Cf. H 2S ex GYY4137 combats
respiratory syncytial virus airway infection PMID 27314446;; cf. also Bazhanov N et al. SciRep 7 Art No.
41029(2017); active against H1N1).

For clinical trials of antivirals may need to take account of patient’s in vivo road dust antiviral load.

Does sulphonamide H2N-Ph-SO2NH2 interact synergistically with H2S?

Will likely react with nitric oxide.

Reaction of sulphonamide with phosphorous acid or pyrophosphorous acid -> VV.

Benzothiazole-2-sulfonamide (antiviral?)

7-3.
Dimethyl Sulphide
A major marine sulphur source occurring in small
amounts in the atmosphere
Is possibly antiviral;
Occurs in small amounts together with a range of other
sulphur containing molecules of possible antiviral
interest in oak barrel aged wine and
Scotch whiskey
Dimethylsulphide transforms in the atmosphere into
HOOCH2SCHO (cf. PNAS 2020 117 (9) 4505-10),
[Could be antiviral?]
and likely also further transforms into via oxidation->
DIMETHYLSULPHOXIDE (DMSO)
(CH3)2)S=O.
DMSO may have direct antiviral and also additional
antiviral action via anti-syncytium effect.
DMSO was originally thought to be inert biologically (so
was used as a vehicle for drugs) but was later found to
have a major effect per se on DNA replication (acting
like a mRNA?) and potentially also eliciting a potentially
potent anti-viral effect.
DMSO has been reported in blogs to provide health
-benefits. Anti-arthritic. Also apparently pro-health
neurological effects. Can apparently be given e.g. as an
oral drug in conjunction with ascorbate
Reported anecdotal benefit rubbing on skin to get
highly systemic benefit.
Antiviral for herpes. (HSV-1 cf use of Acyclovir for HSV-
1 (cf. PMID 12052246). Can greatly (solvent effect)
increase effectiveness of Acyclovir action. Allows
better skin penetration. Effect likely to
be more than this however.
Also beneficial for AD. Putative an anti-AD therapy.
Delivered as nasal aerosol as has been reported for heparin...(Cf. C Vancheri et al J Allergy Clin Immunol 2001
108 (5) 703-8

8.
MORE ON
Possible Nasal Aerosol Delivery of Antiviral
drugs
surely is a critical measure for global
pandemics which threaten the human
species
Cf. PMID 20406083.

Aerosol delivery may benefit current and future pandemic threats using the broad-spectrum antivirals
For a list of possible antibiotic substances which might (in small amounts) be considered as part of a aerosol
cocktail, see the listed antiseptics in PMID 9880479 (McDonnell & Russell 1999).

Add to this conventional antibiotics and antivirals.

Consider VAPING them?

Could

Polyarylsulfones have antiviral properties? Needs to get tested!

Also consider adding the following substances in the nasal spray cocktail

Curcumin (cf. PMID 31130924) Inhibits Influenza A virus, Hepatitis virus, Respiratory Syncytial Virus, Dengue virus, Herpes simplex,
Papilloma and also inhibits HIV (but a curcumin boron complex is apparently more active).

Sulphonated Lignin derivatives also have broad spectrum antiviral activities.

Tamoxifen which demonstrates a broad spectrum anti-infectivity, including antiviral activity. Counters HIV, HCV, HSV, Ebola

Incl. via NFκB and prevents activation of RNA polymerase.

Selenium-based (potential) antivirals

Aza analogues of Ebselen PMID 15544790 are antiviral, antimicrobial and antifungal.

Ebselen is also anti-Alzheimer’s disease (cf. PMID 28502066). It seems that viruses may contribute to AD aetiology.

Selenoprotein-P (antioxidant) may interact positively with antiviral heparan sulphate (cf. PMID 19345254).

Antiviral diphenyldiselenides PMID 28604620 (2017); Cf. 14630233.

Selenocysteine + rifampicin PMID 7241092 for inhibition of influenza A;

Cf. selenazfurin counters influenza A and B, PMID 3729336 and 6517540.

Dietary Se supplementation etc., counters influenza etc. cf. PMID 31487871

Se is involved centrally in antioxidant defence.

Selenoproteins in ER Involved in HIV (may have encoded seleno-protein).

General Se over-supplementation, however, may encourage increased rate of viral mutation. Especially to RNA viruses?

Selenium dietary supplementation is however generally antiviral e.g. against Hepatitis B, C and possibly also HIV-1.

N.b. Ebselen is potentially a key Se drug.

Urea-Related H2S- inducer potential antivirals

Metformin, possible antiviral effect; PMID 29363663 via increasing insulin sensitivity;

(conceivably could also cause an increase in H2S concentration cf. PMID 23950598).

Cf. also Metformin reported on web to Inhibit HIV-1 Dengue Zike Ebola Influenza H1N1)..

Thiourea.

Cf. non-nucleoside HIV reverse transcriptase inhibitors PMID 15964195.

Uric Acid may also be a cofactor in some ethnic groups for hepatitis C viral induced liver fibrosis damage (cf. PMID 30395654)

9.
FOOTNOTES
(Other topics which need more research into re COVID-19)
ANTIVIRAL 2´,5´-oligoadenylate (-5A) synthetase discussed by Kenney de Meirlier at 2003 Chronic Fatigue Syndrome

Roy Soc Edinburgh workshop 2003; RNAse L. Cf. possible IFN therapy for COVID-19 ?

Cf. Alpha 2B Interferon therapy likely to be antiviral etc.

cf. Glasgow University researcher Helen Yaffe comment on Cuban research induced enhancing RNAseL to combat COVID-19 (in China
where the Cuban drug is manufactured).

Other antiviral systems might be similarly enhanced by Interferon to combat COVID-19.

Aerosol format. Boosts immune system to combat COVID-19.

(Cf. LC Cham et al. Pharmaceuticals 2019 12 142)?

Micro RNA screen cf. PMID 28148804

mR-532-5p : antiviral activity

Identification of wnt signalling during Flavivirus infections

9-a. CONVENTIONAL ANTIVIRAL DRUGS & COVID-19

T Smith, J Bushek, A LeClaire T Prossser “COVID-19 Drug Therapy” Elsevier (Lancet)

includes lmw heparin

discusses chloroquine and hydroxychloroquine

Lopinavir – Ritonavir,

Remdesivir and

Favipiravir

Cf. although SARS and MERS have 82% homology w COVID-19

such conventional anti-viral therapy PMID 27281742; 32127666

does not seem to work for COVID-19

i.e. by using anti-HIV Nucleoside Analog Anti-Virals.

Cf. NEJM Mar 18 2020 B Cao et al. ;

Protease inhibitors cf. N Chen Lancet Feb11 2020.

But cf. A King, Chem World April 2020 wrote that ‘Detailed 3D coronavirus spike map offers hope for
vaccine development’ paper in bioRxiv shows a Sars-CoV-1 antibody finding potently to the spike
protein of the novel coronavirus via Human monoclonal antibody m IgG.

Possible synergy between COVID-19 with influenza viruses? This may cause difficulty in identifying COVID-19s cf Wu X et al Emerging
Infect Dis vol 26 No6 June 2020.

However, it was reported in 2018 (Gaiuai et al.) that the viral polymerases in SARs-COV-RdR8 are successfully inhibited by a modified
nucleoside phosphonate approach.

Further guidance to gain a broad spectrum antiviral via modifying nucleoside analogues for COVID-19 therapy was given by Ju et al. in
bioRxiv in the context of 98% similarity between SARS-CoV and SARS-CoV-2RdRps at doi:https://doi.org/10.1101/2020.03.12.989186

N.b. Acyclic nucleoside phosphonates are likely to be the key class of antiviral drug (via inhibition of nucleic acid synthesis) forant-COVID-
19 cocktail.

(Cf. PMID 16264436).(Cf. tenofovir for the prevention of AIDS). The non-mammalian phosphonate with P-C replaces the P-O-C groups
needed to allow nucleic acid polymerases to function.

RSC Chem World April 2020 A King, “Detailed 3D coronavirus spike map offers hope for vaccine development”

“The spike is what we want to try and target with vaccines).

New broad-spectrum antivirals (including their presence in multi-drug therapies); may be a better ploy
to combat present and future pandemics:

e.g. by repurposing use of known anti-cancer drugs bound to polymeric potential

antivirals cf. PMID 32214933.

The logic is that since anti-cancer is also anti-nucleic acid biosynthesis that this is potentially
antiviral. Hence should test cancer therapeutics for antiviral activities.

Some very simple antiviral procedures may, however, also be useful. Cf. following sections.

9-1.
SALT WATER mouthwash and gargle (also
aerosol spray?) for antiviral THERAPY Nasal and
throat irrigation to combat COVID-19?

Reported in the Scotsman newspaper. Edinburgh study (ELVIS) headed by academic virologist S Ramalingam how ancient
use of salt (NaCl, e.g. pristine seawater) water (nasal irrigation) combats viral diseases.

Danger if use real modern seawater of pollutant induced disease.

Nevertheless it is of relevance to the COVID-19 pandemic to note that:

 -
All viruses are apparently inhibited or eradicated via hypochlorite (Cl-O )
generated from the chloride anion. Cf. S Ramalingam Sci. Rep. Art. No. 1015 (2019) (PMID 30705369) which examined
influenza A and B parainfluenza, meta-pneumonia, rhinovirus, bocavirus, coronavirus, mycoplasma etc depletion under
Cl- induced hypochlorite. This seems to have been a successful preliminary, n=68 study (a larger cohort seems to be
needed however) of hypotonic saline nasal irrigation (chloride-ion dependent innate antiviral response) and gargling for
the common cold may be adapted as a preventive measure for

the coronavirus COVID-19 infection.

NaCl may produce sufficient Na hypochlorite (bleach) to kill viruses in airways.

Danger of damage to host from use of hypochlorite needs to be considered.

The skin and other tissues however adapt their HEPARAN SULPHATE biosynthesis is to balance
outer salinity.

[Nb. Need to avoid danger of forming perchlorate which blocks heparan sulphate sulphation].

This phenomenon was first observed by Nader et al. in 1983 and confirmed by Olde et al. in 2019. These experimental
studies offer novel insight into a major mechanism of osmoregulation by the vasculature and skin cf. PMID 31365577. If
sodium chloride concentrations are increased for sufficiently long at the mouth, throat and lung surfaces, it is apparent
that the predicted increase in the length of antiviral side-chains of sulphated heparan proteoglycans will confer

as well as an added anti-viral boost to the

increased general tissue protection

surfaces which meet viruses. A good biochemical mining situation.

Traditional use of ammonium chloride tablets for bronchial and throat infections (I believe this was the case) may have a
similar biochemical basis.

9-1-1.
Ammonium Chloride (used traditionally) which on dissolution produces chloride anions. is
also presumably capable of producing hypochlorite under in vivo conditions and hence may kill viruses under specific to be
identified condition.

9-1-2

PAW water for COVID-19 (scam? This would be a common thought. But need to check out)

Web and US journal reported (Taiwan) therapy: PLASMON ACTIVATED WATER (PAW) THERAPY. PMID 29843406

Claimed anti-microbial effects. If made with gold mesh could actually be a form of ultra- trace (homeopathy-like)
nanogold particle therapy? Could in the future be shown to be a form of nanoparticle therapy.

FOOTNOTES continued

Need more research into

A terpenoid H2S generator: thiolan.e
Convalescent Plasma Cf. J Med Virol. L Zhang & Y Li, 13 Feb 2020.

Potential interventions for novel coronavirus in China;

Meta analysis of literature showed up NEED FOR

Convalescent Plasma antigens is indicated for COVID-19 intervention in patients.

10. Another thought Cow’s milk antigens might allow for a mass-produced antigen protein database;
allowing creation of a larg- scale antiviral antibody library.

If cows are infected with COVID-19 then they will potentially develop good immunity to this virus.

Cow milk antigens might also protect humans.

Possible Ploy: breed dairy cows exposed to COVID-19 and use their milk to protect humans from COVID-19 infection.

Why are babies, infants and children less affected by the COVID-19 virus? Maybe dietary

MILK protects against COVID-19 to some extent? Use of milk is less in China but more in Finland and Norway.
May reflect public spread of the virus.

Do most babies have antibodies to related viruses?

MILK (especially human) is known to contain a battery of anti-virals.

Cf. Haiyan Sun & Håvard Jenssen DOI: 10.5772/50158 (“Milk Derived Peptides with Immune Stimulating Antiviral
Properties”).

[Via regulation of innate immune response and down regulation of sepsis generating conditions; also direct
single substance (e.g. lactoferrin and lactoperoxidasee antiviral actions against HIV Herpes simplex, RSV,
echovirus; cf. oral admin of lactoperoxidase attenuates influenza virus. Lactadhedrin inhibits rotavirus; beta
lactoglobulin prevents gp120 -CD4 host receptor binding. Also Tenascin C, vide infra.

A puzzle as to why HIV-retrovirus infected breastfeeding mothers seemed not often to pass on the virus to their offspring
found that human milk proteins (e.g. Tanascin-C a heparin/heparan sulphate binding wound healing protein were also anti-
virals. They may work in concert with immunoglobins etc. Cow’s milk seemed at first not to be anti-HIV. Later data seems
to throw doubt on this. Milk varies in quality. The best milk may have broad spectrum antiviral activity. Worth looking
into for COVID-19. Cf. also “The future of HIV with tenascin C” (A Petherick in SPLASH milk science update February 2015;
Mansosaur RG et al. PLoS ONE 2016 May6 ; PMID 24145401, 27482446).

Do variations in COVID-19 infections between countries and regions and age-groups correlate with MILK consumption? Cf low Chinese per-
capita milk consumption. Perhaps the tendency to avoid milk products especially in educated classes in some Western vegan culture
countries impacts on COVID-19 infection.

Cf. review of milk proteins known to combat a variety of viruses including those which use heparan sulphate for host cell entry.

11.
Mannose Binding Lectin (MBL)
The innate immune response to severe acute respiratory syndrome (SARS) coronavirus (CoV)
infection putatively critically involves the viral glycoprotein interaction with Mannose
Binding Lectin (MBL) [a pattern recognition molecule (capable of genetic polymorphism
which might predict those at greatest risk); MBL is an acute antibody factor before the
specific antibody response. A study of n=561 SARS vs 1188 controls indicated (PMID
15838797) that MBL deficiency is a possible susceptibility factor in the acquisition of SARS
viral infection.
Does this also apply to COVID-19?
A study of MBL in HIV-1 with genotype analysis suggests polymorphism could predict
susceptibility to HIV-1 infection (PMID 19796822).
A study in mice with Ebola virus infection showed that therapeutic recombinant MBL
countered this infection PMID 21288816) thus suggesting how a broad-spectrum antiviral
therapy might be facilitated.
Corpus ID 46424068 In vitro evaluation of the synergistic antiviral effect of ACE-M
{acemannan (a long-chain poly-dispersed beta(1,4) acetylated mannan) with anti-HIV AZT
(azidothymidine) and acyclovir.
The use of mannan adjuvant (100/1 inactivated virus) apparently might (PMID 25887952)
allow pandemics arising from mutation of e.g. H1N1 to be averted by avoiding the otherwise
too-slow development of a new specific vaccine.

11-1.
Banana lectin engineered by replacement of single amino acid to remove mitogenicity but
preserve broad-antiviral activity
PMID 26496612.

12.
More Inorganic chemistry related antivirals
Zinc homeostasis PMID 31632411
is claimed to be a potent antiviral strategy.
N.b.
ZINC chelates to biopolymers, essential in many enzymes .

Serum zinc supplementation for COVID-19 cf. NCT04339556 clinical trial.

ZINC nasal creams are claimed to confer antiviral properties and counter the common cold; cf. meta analysis (PMID 22566526)
HIV infected patients have low serum zinc (Cf. N Fabris et al 1988 JAMA (Letters) 259 (6) 839) thought to be linked to thymic secretory
function reduction in immune function.

Zinc may, together with Calcium especially be relevant for heparan sulphate (antiviral) protein interaction

Zinc chelation inhibits early stages of Dengue virus replication via NFκB, cf. PMID 31632411

Chelation to inhibit bacterial biofilm in mouth etc (may also impact on vires if synergise with bacteria) Use of EDTA PMID 26155384.

Zinc oxide nanoparticles with intrinsic broad-spectrum antiviral activity, cf.

Ghaffani H J Biomed Sci 26 Art No. 70 (2019)

Zinc sulphate + HEPARIN cf.zinc sulphate anti-HSV, PMID 1657829,

HEPARIN-METAL complexes are potential antiviral drugs. I.e.

PALLADIUM, Rhodium + Heparin like polymers are potential antivirals

SILVER nanoparticles are potential antiviral agents cf. PMC 6264685 PMID 22024958 (also discusses nanoparticles of other elements, Cu,
Zn, Ti, Mg, Au as well as Ag).

These could be coupled to heparin or other anionic polysaccharides or milk protein derivatives.

13. The Linus Pauling anti-common cold high-ascorbate dietary

or medically administered i.v. supplementation hypothesis.

Cf. the abovementioned role of ascorbate in the NO-H2S

crosstalk shed new light on Pauling’s Old Ideas.

A possible additional explanation for the putative broad spectrum anti-viral effect of high dose ascorbate is the upregulation of heparan
sulphate (HS) biosynthesis by ascorbate to yield heparan sulphate chains with increased sulphation, [cf.Kao J et al. Exp Mol Pathol 1990 53
(1) 1-10; Edward M & Oliver RF, Biochem Soc Trans 1983 111 383 and 112 304].The heparan sulphate sugar chains are the key. [Grant D
Publication-2-web scribd]. An alternative hypothesis is that the core proteins are the key: cf. “ Replication of viruses, Type 2 Diabetes,
Cancer, HSPG, Vitamin C and Xylan : What is the Link? Antonych Ch 2019 researchgate 338214098. This wide-reaching thoughtful paper
shows multiple links between vitamin C cancer and viral infection etc. as does Publicatio-2-web scribd.

Cf. Warburg effect; cf. PMID 27195151. High susceptibility of obese individuals to viral infection may be Warburg related innate immune
phenomenon. Mice studies suggest (PMID 17449587) obesity is associated with higher influenza mortality via impaired immunity.

Back to ascorbate -> heparan (antiviral) idea:

a possible creation of ‘endogenous circulating heparin’ (generated e.g. by endogenous heparinase and nitric oxide) with anti-viral
properties

[This phenomenon had been studied by H Engleberg from the 1960s and suggested to offer therapeutic potential for a range of diseases].

14.
Why do agents which may have beneficial effect in Alzheimer’s disease also possibly inhibit coronavirus infections?

Cf. Chloroquine is reported to inhibit amyloid tau plaque and fibril formation and also to be

a candidate anti-COVID-19 agent. Cf. PMID 32147496; 32171740.

Hydroxychloroquine is less toxic but of apparent similar efficacy.

Could this be because amyloid fibrils can aid viral entry to the host? This has been reported for HIV infection.

Cf. “The surprising role of Amyloid Fibrils in HIV Infection PMID 24832047.

15.
SULFONAMIDE antivirals

Known as antibiotics (antibacterial and antiprotozoal)l

(cf. antiviral sulphonamide drugs PMID 14965291) Perhaps should be revisited for coronaviruses?

Parent structure is H2N-Ph-SO2NH2 .

16.
POLYINORGANIC PHOSPHATEs (PolyPi)
Can be manufactured simply by dehydrating
phosphoric acid. This may be accomplished by acetic
anhydride.
Are Potential RNA Antivirals. (Cf. Jean Philippe St-Pierre PhD Thesis Toronto 2011 brief mention of antiviral activity of
PolyPi)

The Nobel laureated Arthur Kornberg who discovered the mechanism of DNA biosynthesis
in 1942 also later in life, postulated that PolyPi preceded DNA and RNA in the evolution of
biota. PolyPi had enabled the original biosynthesis of nucleic acids making up RNA and DNA
This could also by why these polymers still occur (abundantly) on all modern biological cells
(including bacteria) and seemingly also organelle surfaces. They, like nucleic acids, are
apparently ‘essential for life units’. They do not seem today to create new nucleic acids.
They are missing from viruses. But why are PolyPi still needed by the bacteria and other
non-viral species? According to Brown & Kornberg (PMID 15520374) PolyPi not only
participated in the origin but also was essential for the survival of species. The modern
organism still needs PolyPi to survive. Perhaps because PolyPi molecules (above a degree of
polymerization of 3) is antiviral [cf. PMID 9052719l There may also be a connection to actin.
PolyPi protein interaction evidently impede viruses perhaps by multiple mechansims.
This should also apply to CIVUD-19
And to novel viruses (calcified nanobacteria) which are not yet accepted as existing.
The calcified nanobacteria which was discovered in Finland, shown to be bogus in the US
but later verified to actually exist by Japanese scientists (PMID 25802705), This may be
where polyPi like molecules come into their own and keep higher organisms safe from the
unconventional virus infection.
PolyPi seems, like heparin, also to bind and serve as a reservoir for a range of other
elements including Si and Ca.
Likely to get PolyPi-SiO2 nanoparticle aggregates.
Review of how PolyPi confers heavy metal resistance to microorganisms: PMID 301817554
Also PolyPi – peptide aggregates [cf J Milner-White & M Russel J Cosmol 2010 3217-25)
Hence polyPi suitably configured may be able to interfere with viral entry or replication.
The work of RN Reusch (PNAS 1988 85 4176-80) showed that polyPi often co-existed with
polyβhydroxybutyrate.
Are at the beginning of understanding PolyP as a major biological system.

16-1.
Could Silicon Biochemistry Help Fight Viruses?

Or are SiO2 nanoparticles similar to viruses and should be avoided.

Do they assist viruses in overwhelming the host anti-viral defences?

Most biochemistry avoids silicon biochemistry.

Might be big mistake.
Silica gel also likely existed in pre-biologically together with PolyPi and may have helped
condense PolyPi from the monomeric H3PO4 in the deep vent . In the lab. Can use acetic
anhydride to make PolyPi from H3PO4. If use H3PO3 instead of H3PO4 get 100 yield of
bisphosphonates which had to get re-discovered in the nineteen sixties (although they were
already known in the nineteenth century). Bisphosphonates often show up as surprising
therapeutics for supposed unconnected illnesses. Started off used for ectopic calcification
then osteoporosis then bone metastasis in breast cancer. May inhibits other cancer. May
have antipathogen activity.
Silicon remains in modern organisms for unknown purposes but seems mainly bound to
(anti-viral) HEPARAN SULPHATE and similar polyanions. Likely some also co-exists with
PolyPi .
Philippa Wiggins (Auckland U) found that silica gel could not only create biopolymers
including PolyPi but also discriminates between D- and L- amino acids and cations Na + and K+
; Mg2+ and Ca2+ likewise.
I.e. silica gel to some extent mimics life. This is without any phosphorus compounds being
present in the gel. The elephant in the room is of course liquid water. Present together
with the other substances discussed here. Silica gel template memory was discovered by
Victorian scientists (personal disc. from a lab manager from the 1960s) who were able to
make silica gel polymerize around specific organic molecule shapes. Templates. This
facilitates molecular separation. Industrial uses of silica gel for precision moulding not
requiring subsequent machining. Silica sols also seem able to behave like templated silica
gel columns and can per se under appropriate pH and heating conditions engaged in some
kind of bio-chemical characteristics. The likelihood that they can disintegrate and form
daughter cells (biological style reproduction of form) is important for a fuller understanding
of the possible origin of life. There are a large varieties of commercial silica sols with
different physical and biological activities. Silica gel particulates putatively predated the
evolution of biologically active PolyPi. Silica gel particulates are capable of altering the
cellular response of viruses as reported in PMID 27547159: the specific SiO 2 studied (which
were insufficiently detailed by the authors) impedes the host antiviral response and causes
cytotoxic insults. The SiO2 nanoparticles used changed the host macrophage gene
expression to decreases the inflammatory responses elicited by the virus. It is like the silica
particles were acting as pro- viruses. This may mean that individuals are inhibited from
mounting an immune response to viral infection dependent on their SiO 2 nanoparticle
loadings (of the digestive system presumably bound to the mucus boundary layers).

Antiviral Polysilicate Esters

?

16-1-1. HINT OF A HYPOTHESIS:

SILICA synergies with viruses e.g. those in the
gut to enhance viral infection of the lungs.
Viral lung damage can be enhanced by the
much-used food additive SiO2 nanoparticles
which apparently can build up in the gut:
Affecting initially the digestive system (and capable of generating
gases which could enter the blood stream) SiO2 nanoparticles
(colloidal particles equivalent to silica sols) are, not as has been
hitherto assumed highly inert particles but, being in some sense
‘alive’ have been found capable of synergy with viral infections which
perhaps may partially explain why some individuals are more
seriously affected by COVID-19 than others?
The difference might be in the amount of dietary induced SiO2 nanoparticles lodged in their
gut which is considered by some to be part of the lung-gut axis. Gut viral infections can
affect the airway and lungs according to the concept (cf. PMID 26892389) that the entire
mucosal system is a single organ consisting of airway, intestine oral and cervical epithelia.

It is evident from the results reported in PMID 27547159 that the

type of SiO2 nanoparticles present in many processed foods could
build up in the digestive system so that different amounts between
individuals dependent on their diets could differently exacerbate
COVID-19 viral infections of the airway and lungs.
The tone of PMID 27547159 is that use of SiO2 in food is a general
threat to public health. This research needs follow up.
That SiO2 nanoparticles are biologically active is not surprising to those who have researched such
particles where biological mimicking effects have been indicated (cf. RK Iler 1979). E.g. for the
haemolysis of erythrocytes SiO2 nanoparticles can be used diagnostically to distinguish osteoarthritis
form rheumatoid arthritis erythrocytes. Differently sized SiO 2 nanoparticles lyse erythrocytes
according to disease. Can also distinguish between erythrocytes of different biological species
according to their differences in erythrocyte SiO 2 sol interaction.

---------------------------------------------------
Cf. also Phosphonates & Related

Phosphonated proteins bind better to aluminium hydroxide adjuvant to increases vaccine potencies (F Lu et al. Vaccine 2013 31 4362.

Phosphorous acid may do likewise.

Phosphorous forms insoluble aluminium carbonate double salts of possible use in vaccines.
Bisphosphonate use as adjuvant like molecule(?)

“Phospho-antigens”.

Zoledronic acid plus IL-2 improved the immunocompetence of HIV-1infected persons (AIDS 23 555) via Vγ9Vδ2 T cells; PMID 1923807.5.

Antiviral activities of adamantyl-containing phosphonous and phosphinic acids, Reznikov AN et al. Russ J Gen Chem 2014 84 1524-30.

Man-Made Organic Polyphosphonates are also known states of matter

Cf. e.g. α,ϖ-disubstituted polymethylpolyphosphonates and polyphenylpolyphosphonates from condensation polymerization

Journal of Polymer Science Part A-1 Polymer Chemistry 1967 5 (1) https://doi.org/10.1002/pol.1967.150050106

The raw bisphosphonates obtained by acetic anhydride dehydration of phosphorous acid, D Grant, Eur Polymer J 1979 15 12 1161-1165
contain oligomers and polymers of possibly useful pharmaceutical properties. May be antivirals

Cf. also use of acetic anhydride to create linked hypophosphate molecules by

Bruno Blaser’s who also found a P-6 Ring-saure (from 1930s research) (O=P-OH) 6.

This could be an antivial.

Another researcher who created a large database of possible antivirals was

MF Lappert (1928-2014) :

could use these scientific publications to get inspiration for possible antivirals.

16-2. more on

POLY-INORGANIC-PHOSPHATE
This (putatively involved-in-early life-and-still-critical-for modern-life e.g. as an energy source for
structuring the extracellular matrix (ECM including heparan sulphate behaviour) and enabling
cognition and memory inter alia) polymer has been reported (in medium to longer chain
forms) to be anti-viral (for HIV) and also anti-syncytium.
It may become defective in age (cf. is reported depleted in AD; polyPi, by removing the most
toxic fibrils (the oligomers by transforming them into less toxic beta sheet fibrils) may
counter a mode of viral entry into host cells.
Does this impact on COVID-19 entry to host cells?

Remember that HIV viruses can enter cells via amyloid fibrils (cf. PMID 24832047) generated from prostatic acid phosphatase and
seminogelins.

Need to know if this scenario is analogous to the disease promotion in AD by the more toxic oligomers from failure of the polyPi
-protection formed less toxic beta sheets.

Is failure of polyPi protection part of how highly infectious viruses enter cells in aged individuals?

It has been recently reported (PMID 30472240) that polyPi 150mer administration protects against lipopolysaccharide induced septic
shock via inhibition of macrophage recruitment.

And that polyPi regulation is a novel therapeutic anti-septic shock strategy.

Could this help COVID-19 induced septic shock?

It is well known that the reaction of acetic anhydride with polyPi monomer, phosphoric acid,
generates polyPi but the same reaction with phosphorous acid generates a library of various
interlinked polyethene hydroxide bis- phosphonates. Get etidronate by hydrolysis. Could such
bisphosphonates substitute for age- or pathogen depleted (?) polyPi?
Could repurposing glyphosate HOC(O)CH2NHCH2P(O)(OH)2
or better its degradation product H2NCH2P(O)(OH)2 (AMPA)
by using these as starting materials for chemical modification
produce polyanionic anti-COVID19 antivirals?
AMPA + Heparin likely has antiviral activity and perhaps less
troublesome anticoagulant activity than UFH.

Inserted Text: KEY TARGET for possible anti-

COVID-19 IDENTIFIED: an anti-calcification
related function of PolyPi which might
suggest a useful broad spectrum drug system
to combat viruses based on specific PolPi
molecular weight.
A ground-breaking study by B Lorenz (1997; PMID
9052719) reported that PolyPi (studied with moderate
polymerization degrees) exhibited a ‘heparin-like
behaviour’ for the inhibition
of HIV-1 replication (at 33.3μg/ml and at higher
concentrations) also blocks syncytium formation.
Short chain PolyPi (less than degree of polymerization
=4) were inactive.
This indicates a possible new avenue of research to
attempt to counter COVID-19.

17. More on Heparin-like Polyanionics-

which are also Broad Spectrum Antivirals .

Cf. e.g. Heparan sulphate mimetics as broad spectrum antivirals, ST Jones et al. Sci Advances 2020 6 (5) eaax938 (modified cyclodextrins)

PMID 32064341.

(Cf..also Muparfostat and Elmiron which mimic heparan sulphate ar (currently available and US FDA approved)

Should be tested for anti- COVID-19 activity).

Can use immediately.

Also polyanion antiviral status is facilitated by HEPARANASE.

Cf. PMID 28927006 Thakkar N et al. (Emerging role of heparinase in viral pathogenesis) (cf. heparanse p53 signaling.)

An older Key heparan sulphate and related ref. ”Polyanions –

A LOST CAUse antiviral strategy??a cflost cause in the fight against HIV aCF.nd other virus diseases” cf.

Cf. Lüscher-Mattli M et al. Antivir. Chem Chemother 2006 Jul 11 (4) 249-59, U Berne.(PMID 10950387) Sulphated polysaccharides and
other polyanion antivirals mentioned need animproved method (e.g. by using nanoparticle delivery) of getting same in vivo activity as that
achieved in vitro.

But the cause may not have been lost!

Lack of H2S causes mispostranl. Heparan Sulphate code assembly. May also be a crosstalking polysulphide
(selenide) code

which act faster than acquired immunity.

Cf. Broad spectrum antivirals may also be obtained from anti-cancer drugs bound to polymers (e.g. polymers
related to Tilorone bound to Pt (cisplatin PMID 32214933 {cf. previous analogous organo-Sn (tin) compound
studies).

Cf. possible similar anti-cancer use of sulphated polysaccharides (cf Farrell NO Ch 4 in Met Ions Life Sci 2018
109-40 deGruyter) could be adapted to create broad spectrum antivirals.

More on Pt-pyrophosphorous acid complex

Platinum POP (a lantern shaped complex of pyrophosphorous [H-P(O)(OH])-O-[H-P(O)(OH) shifted to tri-coordinated P

Pt has unusual energetics. Follow on half lantern complexes with Pt(II) Pt(III).

Shoud checkout its antiviral properties.

Cf. anti-cancer drugs have been shown also to have anti-viral properties.

[During the AIDS crisis sulphated polysaccharides were found to offer broad spectrum antiviral effects against HIV-1 and II and Likely also
effective against respiratory syncytial virus, a major cause of childhood lung congestion/damage; also showed anti syncytium effects
(which could seriously impair conventional B and T cell related immunization) .

It seems likely that the anti-HIV polysaccharides also inhibited a range of other viruses (which like HIV-1 use complex cytokine/chemokine
evasion techniques (cf. PMID 26177523)).

Long list of possible uses against other coated viruses which gain entry via host heparan sulphate.

That (heparin-like) substances with anti-HIV activities may also be effective against heparan sulphate using COVID19 (cf. C Mycroft-West et
al 2020 Noted that the 2019 coronavirus surface protein Spike S1 receptor binding {domain undergoes conformational change upon
heparin binding a possible anti SARS-CoV-2 potential because of their mode of entry to the host is via cell surface heparan sulphate}.

A perceived problem with potential use conventional heparin as a broad-spectrum antiviral is that UFH is also a blood anticoagulant. But
there are available non-anticoagulant heparin including low molecular weight varieties.

Also used for many years, heparinoids such as pentosan poly-sulphate SP54 (Elmiron USFDA approved for interstitial cystitis). This is
obtained from birch wood shavings from which the xylans are extracted using conventional techniques and then sulphated using pyridine
containing medium.

A similar technique applied to marine algal polysaccharides was studied at Aberdeen University round 1990 and a highly active anti-HIV
agent obtained. Sufficient quantities and funding for a clinical trial were however not obtained. A proof of concept was however
established.

An academic study looking at anti-HIV activities of a range of sulphated molecules posted online in 2010

is available at scribd

35999390/

“Old Anti-HIV Study Refs Antiviral Drug Hiv/Aids-scribd”. This lists a range of
starting natural polysaccharides which on sulphation and fractionation might provide the wanted types of antivirals.

Cf. also the document which had listed Aberdeen U research results

Why is PPS Such an Effective Anti NvCJD Agent Revised│ Antiviral Drug Hiv/Aids-Scribd 34916468

Where the anti-HIV-1 activities μg/ml of AZT, sulphated polysaccharides and related substances were compared in a standard assay

compared in a standard assay

Palmaria sulphated polysaccharide fraction 0.25

Polyvinyl sulphate 0.5

Cellulose sulphate 1.0

AZT 1.0

SP54 (Pentosan poly-sulphate) 2.5

Unfractionated heparin 10.

Dextran sulphate 10

[inserted text POLYINORGANIC PHOSPHATE 33.3] Poly inorganic phosphates are intrinsically cheap to produce,[via H3PO4 + Ac2O)
Can also extract from animal or bacterial sources

Pectin sulphate 100

Lambda carrageenan 100

Pullulan sulphate 1000

Raffinose sulphate 1000

De-N sulphohated heparin 1000

[Inserted text
Cf. antiviral Lignin Sulphonic Acid PMID 22558266 Low cost. Broad specificity against HIV strains and other
viruses. Does not stimulate NFκB].

Cf. Modified cyclodextrins (sulphonated with mercapto unidecane sulphonic acid)

to mimic HEPARIN /HEPARAN SULPHATES :broad spectrum, non-toxic to humans antivirals against HIV-2, HSV, RSV,
Dengue and Zica (cf. Jones ST et al PMID 32064341). Active in micromolar concentration range.

The sulphated polysaccharide broad spectrum antiviral avenues were researched by a number of groups internationally (cf. e.g. De Clercq
1990 TIPS 11 198); Clinical trial of low molecular weight heparin in advanced AIDS (1996) showed CD4 stabilized; self-administration was
possible to treat AIDS patients on a long term basis at low cost Chem Abs 125 316373) but eventually was however not pursued twenty
five years ago as alternative highly effective drugs specific for the target virus had been discovered (e.g. AZT[ Zidovudine azidothymidine
nucleoside reverse transcriptase]).

Xylan sulphate is however an approved drug for interstitial cystitis. It also inhibits alphavirus cartilage destruction (thought to be via anti
IL-10 but may also have direct antiviral activities).

Currently Available Anti-viral. Elmiron is an approved drug for interstitial cystitis; (thought to be via anti IL-10 but may also have direct
antiviral activities).

Taurine and taurine -coupled to small molecules

can putatively act as an anti-syncytium (a clumping which lets virus block activities of conventional immunoglobin -based antiviral effects
(as in conventional vaccines).

Heparin and heparin-like anti-virus agents (may include pentosan poly-sulphate (e.g. Elmiron or SP54) which also can potentially also be
anti-syncytium. (Seen for HIV).

The above information could enable a workable antiviral for COViD-19.

18.
Anti-malaria drugs repurposed as antivirals

Chloroquine perhaps better: . Promazine Nicotinamide Emoden or

18-1. Serotonin reuptake inhibitors (but not Statins) show anti-HIV antiviral activity in vivo

Cf. Letendre SL et al. J Neuroimmune Pathology 2007 2 (1) 120-9.

Cinancerin (serotonin reuptake inhibitor).

19.
Other Potential Antivirals

(anti-HIV) Lopinavin and Remesivir;

Nelfisavir Arbidol.

CORONAVIRUS SPECIFIC TREATMENTS doi/10.1002/jmn.25707.

Coronavirus protease inhibitors.

Chymotrypsin and Papain are encoded by coronavirus

Cinaserin Flavenoids Diarylheptanoids

Spike (S) protein related

Domperidone is a gut pro kinetic mediator (cf. PMID 28316536) which may beneficially alter antiviral
gut and blood small mol gas

Benzodiazepines RSV antivirals PMID 16570927,

Angiotensin Converting Enzyme 2 (ACE2) blocker. Cf ACE2 mediates influenza H7N7 acute lung injury

Can block SARS virus entry to host via ACE-2 inhibitors etc C. PMID 23678171

Alpha lipoic acid (a naturally occurring disulphide which enhances glutathione). Anti HIV-1 PMID 1724477.

Steroids. Oestradiol or phytoestrogen; Methylprednisolone PMID 20639272. (e.g. used together with Thymosin a 1

Cf. more male fatalities in SARS-CoD infection.

STEROL REGULATORY ELEMENT binding protein. Potential broad-spectrum antiviral target strategy target

via lipidemic reprogramming (Yuan S et al. Nature Communications 2019 10 Art No. 120 (2019).

POLYPEPTIDES. Mucroporin-M1 (ex scorpion venom) Cationic antimicrobial peptide derived from inactive-as-antiviral Mucroporin by
amino acid substitution has a useful broad-spectrum antiviral activity. Cf. PMID 21620914

POLYCARBOXYLIC ACIDS

Shilajit Indian tradition medicine polyanion (fulvate; similar to soil fulvate (PUTATIVLEY LIKE POLYACRYLATE) which is dramatically good
at inhibiting calcification in vitro and also likely in vivo

Nutritional Intervention for COVID-19

Vit A, B, C, D, E, ω3-PUFA.

[Insert dietary intervention likely impact on heparan sulphate biosynthesis (cf Publication-2 web Grant scribd) a key reverse regulator of
NO and H2S].

Resveratrol (red wine). Cf. PMID 20074034.

Green Tea (polyphenols especially epigallocatechin-3-O-gallate).

Demonstrates a similar broad spectrum strong multi-mechanism antiviral effect to that of curcumin cf. PMID 28805687.

(Influenza, Herpes, HIV, Hepatitis, Ebola, Rotovirus, etc.)

Levamisole. PMID 81635.

Convalescent sera option to combat COVID-19 A Casadevall 2020 J Clin Invest 10.1172/JCI138003 apheresis → blood bank

Cyclosporin A. Cf. PMID 22615963 active against influenza

Gamma Globulin (used during SARS epidemic) injection can boost a person’s immune system

Interferon (IFN) type treatment for COVID-19 infection A Sallard Antiviral Res 2020 08 104791

Traditional Chinese Medicine use of Glycrrhyzn (liquorice roots) Chinese Medicine.

Sulphated glycrrhizin is 4x more effective against HIV (PMID 2443473.

Baicalin. Cf. PMID 24965553. Active against dengue virus.

Cf. Fermented Ginseng. active against a range of influenza viruses PMID 30200514
8-18. Carnosine PMID 20841992 for management of virulent influenza virus by oral formulation of non-hydrolysed carnosine and
isopeptide of carnosine.209. MISC. Cystic fibrosis technique

20. Q : to help drain fluid from lungs in COVID-19 crisis?

Cf. (?)

“How Posture Drainage Can Help” web