by Chandra K. Mittal, Ph.D.
As the Coronavirus (COVID-19) infections are rising rapidly across the world with increasing incidence of morbidity and mortality, the World Health Organization (WHO) has declared it as pandemic. Besides, the negative effects of the viral infections on individual’s health, there is also significant negative impact on the economic health that is being globally experienced with serious societal repercussions in the future.
Ordinarily, epidemics of viral diseases are controlled and treated with vaccines against specific viral pathogens. But with COVID-19 recent emergence in China no readily available vaccine is around. Furthermore, the identification and development of a vaccine being a time consuming process, it is not a solution for the current pandemic. Per Dr. Anthony Fauci, Director of Infectious Disease at National Institutes of Health, most optimistic projection for vaccine availability is about 20 months.
So, the only option left for society is to explore some drug therapy to combat COVID-19 infection. Even though there are several government-approved antiviral drugs available to treat other RNA-genome containing viruses like the COVID-19, none of these have been tested or approved for patients infected with COVID-19. Besides, such testing will take about 24 months to complete which cannot be helpful in the current pandemic.
In the meantime, there is urgency to control the COVID-19 pandemic and treat those virus-infected patients who face serious aliment or death. Society needs to come up with some drug intervention that it can be speedily tested on humans in relatively short span, safe for human use, and can be speedily approved by the government agencies around the world.
At the moment there are two drugs, Statins (e.g. Lipitor) and Chloroquine that are worldwide available, safe, government-approved for other ailments but not COVID-19. But these have tested in experimental models and been shown to have antiviral activity to prevent the spread of the disease.
Research studies conducted with Statins or commercially available cholesterol transport inhibitor, U-18666A on cell-culture systems, animal models and Human subjects have shown that these drugs/compounds reduce the entry of viruses into the host cells protecting them against the viral cytotoxicity. These include Influenza virus [Biomedical Research International, Vol. 2014; ID 872370], [Antiviral Research. vol. 145, 96-102, (2017)]. In these studies, the protective effects of cholesterol-inhibitors on host-cells were reversed by the addition of cholesterol, indicating the requirement of cholesterol for viral infection.
Converse has also been observed with cholesterol, which is reported to promote infection by viruses like Human Immunodeficiency Virus (HIV) [J. Leukocyte Biol. V. 80, 1044-1051 (2006)], Hepatitis C Virus (HCV) [PLoS Pathogens v. 3 No. 8, pp 1017-1022 (2007)], Hepatitis B Virus (HBV) [J. Virol. 85 (24) 13373-133383 (2011)], Hantavirus [PLoS Pathogens. V. 10 (2) (2014), and Ebola Virus [Nature v.477 (7364): 340–343 (2012)]. Coincidentally, all these viruses are single-stranded (ssRNA) viruses with good degree of nucleotide homology which may account for their common mode of host entry and high infectivity.
Similarly, another drug Chloroquine, approved for malarial infection and inflammatory disorders like rheumatoid arthritis, has been also studied for its antiviral effects on Human coronavirus. Results with studies in cultured cells indicate that Chloroquine is almost 1400 times more effective in inhibiting the coronavirus than killing the host cell. This indicates the high safety margin for chloroquine in neutralizing the virus. [Antimicrob Agents Chemother. 2009 Aug; 53(8): 3416–3421].
Similar pattern of antiviral activity of hydroxychloroquine have been also recently reported in another study with Monkey kidney cells [Clin Infect Dis. 2020 Mar 9]. Chloroquine and Hydroxychloroquine have been also tested in Human trials for their effect on HIV-1 infection, and have been found to curtail the infectivity of the virus [Lancet Infect Dis 2003; 3: 722–27]. A study with cell-cultures and mice model also showed significant antiviral activity of chloroquine against the Zika virus infection, which was attributable to lack of viral entry into the host cells [EBioMedicine 24 (2017)189–194].
Thus, there is good body of scientific and anecdotal evidence and rationale to justify the use of Statins and Chloroquine to evaluate the preventive and therapeutic potential of these drugs on coronavirus infection in the current pandemic situation. Besides, these drugs are less toxic to hosts than the classic approved antivirals drugs which either interfere with expression of viral genome or inhibit enzymes that are critical for the survival of the host cells. Statins and Chloroquine, on the other hand, block either the entry of the virus into the host cell or create a local intracellular environment like acidification inside the host cell, which incapacitate the virus without destroying the host cell. This limits their toxicity.
In addition, Statins and Chloroquine are already approved drugs by governments worldwide for other ailments, and can be easily “repurposed” with relatively less human testing and regulatory burden. These drugs are also mass-produced, so these could be cost-effective for governments and the consumers, especially in the Less Developed Countries (LDC).
There is urgent need to initiate more aggressive research on human trials for Chloroquine-Statin combination to prevent or treat COVID-19 infections in countries with high populations, including the United States, China, Italy, India, Iran, etc. Because of their different modes of actions, the combination of Statin and Chloroquine is likely to be more efficacious due to physiological synergism with high safety.
At this point there are only very limited human studies underway to treat COVID-19. One patient studies have been recently initiated in China on Chloroquine-Remidesivir combination on Chinese population, but this may be of limited value for the world. Per the US Govt. website www.ClinicalTrial.gov, two other studies at University of Oxford and Thailand are planned but yet to be initiated, and will be completed in about two years.
In challenging times like the current COVID-19 pandemic, the world needs to come together under the aegis of the World Health Organization (WHO) and try to find quick and inexpensive solution to protect the human society at large. The potential of Statins and Chloroquine to protect against the coronavirus infection can make them the prophylactic drugs of choice. It is time for world governments to take the bold initiative and step up to the challenge.
Dr. Chandra Mittal is Professor of Bio-Medical Sciences at Houston Community College System, Houston, and Co-Founder of Indo-American Association Houston. He can be reached at email@example.com.