Based on a novel anti-viral-pandemic theory, we propose that taking paracetamol and vitamin C or ibuprofen and vitamin C every day could be a very simple way to prevent COVID-19. To prove the effectiveness of these drug combinations, urgent clinical trials should be done.Mass prophylactic-drug administration might not provide 100% protection, but can reduce coronavirus deaths and severe cases, which might facilitate success of natural herd immunity. This herd immunity could be named as "drug-escort-natural herd immunity ".

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1

Taking Paracetamol and Vitamin C or Ibuprofen

and Vitamin C Every Day Could Be a Simple

Way to Prevent COVID-19

Gao-De Li

Email: gaode_li@yahoo.co.uk

After the COVID-19 pandemic outbreak began, people were told that

paracetamol or ibuprofen can only be used to treat the symptoms of

COVID-19 , but we think that taking paracetamol and vitamin C or

ibuprofen and vitamin C every day could be a very simple way to prevent

COVID-19. This idea is based on a novel anti-viral-pandemic theory

proposed recently by us [1]. The key points of this theory are: Viral

infection is cell-type specific and the cells infected by virus is called the

viral target cells. The reason why a virus can infect its target cells is

because the target cell's gene expression pattern is suitable for the viral

infection. Gene expression pattern in a cell type is determined by 3D

genome architecture and genotoxic agents (including chemical, physical

and biological agents) are only agents that can be used to alter 3D genome

architecture. We think that some old drugs with genotoxic side effects

could be used to temporarily alter 3D genome architecture in the viral

target cells so that the gene expression pattern in the viral target cells could

be temporarily altered, which might reduce the target cell's susceptibility

to viral infection, enabling the viral target cells to temporarily become 'non-

viral target cells'. This strategy could be used to prevent all viral infections

including infections with variant viruses. Currently, all reported drugs that

2

show preventive and curative effects on COVID-19 have genotoxic side

effects, which strongly supports our anti-viral-pandemic theory.

Paracetamol, ibuprofen and vitamin C are old less-toxic drugs with

possible genotoxic side effects [2][3][4], which could be daily used by

everyone for preventing COVID-19 without health authority permission.

To prove effectiveness of these drug combinations, urgent clinical trials

should be done. Those who cannot take paracetamol and ibuprofen could

take vitamin C and turmeric or vitamin C and berberine because both

turmeric and berberine possess possible genotoxic side effects [5][6]

and are so safe that they could be served as prophylactic drugs for long-

term use.

In addition to the drugs or supplements as described above, there are

numerous antimalarial drugs with genotoxic side effects, such as

chloroquine, hydroxychloroquine, mefloquine, primaquine, amodiaquine,

lumefantrine, artemether, artesulate, and pyronaridine etc. All these drugs

could be used to prevent COVID-19, but their safety for long-term use

should be taken into account. We predict that compared to non- malaria-

endemic regions, the number of COVID-19 cases is much smaller in

malaria-endemic regions in which many people take antimalarial drugs to

prevent malaria. We also predict that during the pandemic period, cancer

patients who are taking less-toxic genotoxic anticancer drugs are much less

likely to suffer from COVID-19 than cancer patients who didn't receive

chemotherapy. In a word, we believe that only drugs or supplements that

are genotoxic to the coronaviral target cells, such as epithelial cells of

respiratory system could be used to effectively prevent and treat COVID-

19.

3

Based on our theory, repurposing old drugs for preventing COVID-19

could be done by anyone who can perform Google search. The guidelines

for doing this are very simple. First, the old drugs must be safe and could

be used for long time; second, the old drugs must have genotoxic side

effects based on genotoxicity testing; third, to increase chances of success,

drug combinations must be used, i.e., don't use a single drug for preventing

COVID-19. The best drugs are those that are safe for long-term use and

show specific genotoxicity in epithelial cells of respiratory system.

Unfortunately, it is difficult to find these cell-type specific genotoxic drugs

in near future. Therefore, at present, to prevent COVID-19, we have to use

non-specific genotoxic drugs that may be genotoxic to various cell types

including epithelial cells of respiratory system.

Since there is uncertainty in COVID-19 vaccine and anti-coronavirus drug

developments, repurposing old drugs with genotoxic side effects for

preventing COVID-19 will play a very important role in the containment

of COVID-19 worldwide. Therefore, we are appealing for mass

prophylactic-drug administration in all COVID-19 seriously-affected

countries to curb the COVID-19 pandemic. For mass prophylactic-drug

administration, we recommend 2 drug combinations: No.1. Vitamin C (500

mg) + paracetamol (500 mg), once a day for 2-3 weeks; No.2. Vitamin C

(500 mg) + berberine (400 mg), once a day for 2-3 weeks. The two drug

combinations can be alternately used for long time.

Taking prophylactic drugs might not provide complete protection, but can

reduce coronavirus deaths and severe cases， which might facilitate the

success of natural herd immunity that is a key to defeat COVID-19

4

pandemic globally. This herd immunity could be named as " drug-escort-

natural herd immunity".

References

[1] Li, G. D. (2020) Non-Carcinogenic Genotoxic Drugs Could Be Used

to Prevent and Treat COVID-19. Open Access Library Journal, 7: e6536.

https://doi.org/10.4236/oalib.1106536

[2] Dybing, E., Holme, J.A., Gordon, W.P, Søderlund, E.J., Dahlin, DC;

and Nelson, S. D. (1984). Genotoxicity Studies with Paracetamol. Mutat

Res, 138, 21-32. doi:10.1016/0165-1218(84)90081-8

[3] Philipose, B., Singh, R., Khan, K.A. and Giri, A. K. (1997)

Comparative mutagenic and Genotoxic Effects of Three Propionic Acid

Derivatives Ibuprofen, Ketoprofen and Naproxen. Mutat Res, 393 , 123-

131. doi:10.1016/s1383-5718(97)00095-8

[4] Nefić, H. (2008) The Genotoxicity of Vitamin C in Vitro. Bosnian

Journal of Basic Medical Sciences, 8 , 141-146. https:// doi.org/ 10.

17305/ bjbms. 2008.2969

[5] Cao, J., Jiang, L.P., Liu, Y., Yang, G., Yao, X.F.and Zhong, L.F. (2007)

Curcumin-Induced Genotoxicity and Antigenotoxicity in HepG2

cells. Toxicon , 49 ,1219-1222. doi:10.1016/j.toxicon.2007.02.006

[6] Pasqual, M.S., Lauer, C.P., Moyna, P. and Henriques, J. A. (1993)

Genotoxicity of the Isoquinoline Alkaloid Berberine in Prokaryotic and

Eukaryotic Organisms. Mutat Res , 286 , 243-252. doi: 10.1016 / 0027-

5107(93) 90189-m

5

Realization of Unintended "Herd Chemoprotection" Might Be the

Main Reason Why COVID-19 Pandemic in African Countries Is Not

So Severe

Gao-De Li

Email: gaode_li@yahoo.co.uk

COVID-19 Pandemic in African countries seems not severe, which has

puzzled many people including medical scientists. Several reasons have

been proposed to explain this phenomenon [1], but we don't think that they

are convincing. In this short article, we would like to present a different

explanation.

Based on our anti-viral pandemic theory, any drugs with genotoxic side

effects could be used to prevent COVID-19 [2][3]. The main reason why

COVID-19 pandemic is not severe in Africa is because most people in

African countries are taking different drugs all year round to prevent or

treat various infectious diseases, such as malaria, filariasis, and HIV

infection etc. All these drugs have more or less genotoxic side effects and

thus could be effective in prevention of COVID-19. This phenomenon is

quite like mass drug administration for preventing COVID-19. In a word,

the anti-pandemic success in Africa is attributed to unintended mass

prophylactic-drug administration.

Large portion of population becoming immune to an infectious disease is

called herd immunity which can block the disease transmission within the

population. Similarly, large portion of population taking prophylactic

drugs against an infectious disease could be named as "herd

6

chemoprotection" wh ich can also block the disease transmission within

the population. "Herd chemoprotection" might not provide complete

protection, but could reduce coronavirus deaths and severe cases, which

may facilitate success of natural herd immunity . This herd immunity could

be named as "drug-escort-natural herd immunity" [3] . Besides, compared

to herd immunity, "herd chemoprotection" is easier to achieve. If 'herd

chemoprotection' (just mass administration of vitamin C and low-dose

paracetamol) in every country had been realized at the early stage of

current COVID-19 pandemic, millions of lives could have been saved and

the pandemic would have been ended within few months. Unfortunately,

in this world- wide anti-COVID-19 battle led by WHO, mass prophylactic-

drug administration or "herd chemoprotection" has been neglected.

In conclusion, to end COVID-19 pandemic, "herd chemoprotection" is

paramountly important because it can not only block virus transmission,

but also contribute to success of natural herd immunity which is better

than herd immunity realized by unsafe and ineffective vaccination.

References

[1] Njenga MK, Dawa J, Nanyingi M, Gachohi J, Ngere I, Letko M, Otieno

CF, Gunn BM, Osoro E. Why is There Low Morbidity and Mortality of

COVID-19 in Africa? Am J Trop Med Hyg. 2020 Aug;103(2):564-569.

[2] Li, G. D. (2020) Non-Carcinogenic Genotoxic Drugs Could Be Used

to Prevent and Treat COVID-19. Open Access Library Journal, 7: e6536.

[3] Li, G. D. (2020) Taking Paracetamol and Vitamin C or Ibuprofen and

Vitamin C Every Day Could Be a Simple Way to Prevent COVID-19

DOI: 10.13140/RG.2.2.34686.61769/7

... Based on our anti-viral pandemic theory, any drugs with genotoxic side effects could be used to prevent COVID-19 [2] [3]. The main reason why COVID-19 pandemic is not severe in Africa is because most people in African countries are taking different drugs all year round to prevent or treat various infectious diseases, such as malaria, filariasis, and HIV infection etc. ...

... "Herd chemoprotection" might not provide complete protection, but could reduce coronavirus deaths and severe cases, which may facilitate success of natural herd immunity . This herd immunity could be named as "drug-escort-natural herd immunity" [3]. Besides, compared to herd immunity, "herd chemoprotection" is easier to achieve. ...

  • Gao-De Li Gao-De Li

This short article states that realization of unintended "herd chemoprotection" might be the main reason why COVID-19 pandemic in African countries is not so severe.

  • Gao-De Li Gao-De Li

Three-dimensional (3D) genome structure plays an important role in the regulation of gene expression. Alteration of 3D genome structure can change cell's gene expression pattern that causes cellular function change and thus could be used as a novel therapy for treating many diseases including COVID-19. Genotoxic drug is the only drug that could be used to alter 3D genome structure. Since at present no purpose-made non-carcinogenic genotoxic drugs for altering genome structure are available and fighting COVID-19 must be done without delay, it is possible to repurpose some old drugs as non-carcinogenic genotoxic drugs that can be used to reduce target cell's susceptibility to SARSCoV- 2 which causes COVID-19 and to modulate immune cell's response to SARS-CoV-2 infection through altering 3D genome structures in target cells and immune cells.

Three months since the detection of the first COVID-19 case in Africa, almost all countries of the continent continued to report lower morbidity and mortality than the global trend, including Europe and North America. We reviewed the merits of various hypotheses advanced to explain this phenomenon, including low seeding rate, effective mitigation measures, population that is more youthful, favorable weather, and possible prior exposure to a cross-reactive virus. Having a youthful population and favorable weather appears compelling, particularly their combined effect; however, progression of the pandemic in the region and globally may dispel these in the coming months.

Paracetamol and its major ultimate reactive metabolite, N-acetyl-p-benzoquinone imine (NAPQI) were studied for their genotoxic potential. Neither paracetamol nor NAPQI were found to cause mutations in Salmonella typhimurium, whereas NAPQI was severely cytotoxic to the bacteria. Radiolabelled paracetamol was found to bind covalently to DNA added to mouse-liver microsomal incubations at a rate of 2.6 pmoles/mg DNA/min. Paracetamol also bound covalently to hepatic DNA at a level of 15 pmoles/mg DNA after a hepatotoxic dose of paracetamol to mice. NAPQI caused extensive DNA single-strand breaks as evidenced by alkaline elution of DNA from treated Reuber hepatoma cells. This effect occurred at concentrations which later resulted in cytotoxicity. Paracetamol was shown to induce increased DNA-repair synthesis in isolated mouse-liver cells in monolayer culture, at concentrations where also cytotoxicity was evident. Increased DNA-repair synthesis occurred at lower paracetamol concentrations in cells isolated from mice pretreated with phenobarbital. Taken together, these data show that paracetamol can cause DNA interaction leading to damage at levels which are cytotoxic.

The mutagenicity of three propionic acid derivatives, namely ibuprofen, ketoprofen and naproxen, was tested in the Ames mutagenicity assay (in strains TA97a, TA100 and TA102) and in vivo genotoxicity was tested by sister chromatid exchange (SCE) in bone marrow cells of mice. These are the anti-inflammatory drugs frequently used in different parts of the world. Mutagenicity results showed no mutagenic effects in strains TA97a, TA100 and TA102 for all three drugs. Results of in vivo SCE assays indicate that these three drugs are weakly genoxic in bone marrow cells of mice. This is the first report of the Ames mutagenicity assay for ketoprofen and in vivo SCE assay for three drugs.

Curcumin, a polyphenolic yellow pigment found in turmeric, is commonly used as a coloring agent in foods, drugs, and cosmetics. In our previous study, we found that low levels of curcumin did not increase the reactive oxygen species (ROS) formation and caused no damage to DNA in human hepatoma G2 (HepG2) cells, but at high doses, curcumin imposed oxidative stress and damaged DNA. In the present study, we are determined to investigate the genotoxic and antigenotoxic effects of curcumin using HepG2 cell line, a relevant in vitro model to detect the cytoprotective, antigenotoxic, and cogenotoxic agents. The results of micronucleus (MN) assays showed that, on one hand, curcumin at the high tested concentrations (8 and 16 microg/ml) displayed a small but significant increase in the frequency of MN, and on the other hand, it was observed that the low tested concentration (2 microg/ml) significantly reduced the MN formation induced by the chemotherapeutic agent cyclophosphamide. The present results indicate that curcumin shows both genotoxicity and antigenotoxicity depending on its concentration.

  • Hilada Nefić

The genotoxic effects of Vitamin C (ascorbic acid) on human lymphocytes in vitro were estimated by analyzing and identifying various chromosome abnormalities, in relation to the concentration of Vitamin C. Testing concentrations of Vitamin C induced different aberrations including the impairment of spindle function. The spindle disturbances can result in mitotic arrest, multipolar spindles and multipolar segregation, errors in chromosome segregation, formation of chromosome bridges and chromosome laggards. The most frequent irregularities were found in anaphase and telophase. A certain number of lymphocytes were arrested at anaphase or telophase (in colchicine-untreated cultures of human lymphocytes). Testing concentrations of ascorbic acid did not induce a significant increase in the number of aneuploid mitoses and were not clastogenic except at the highest concentration (1,000 microg/ml) in colchicine-treated cultures, and in colchicine-untreated cultures of human lymphocytes the pulverization of chromosome was observed. Vitamin C changed the mitotic index value of lymphocytes notably at the higher concentrations (250, 500 and 1,000 microg/ml).