COVID-19: Present remedies and link to Air Pollution

Student Contributor: Soham Biswas

In December 2019, while the Christmas Eve was approaching near, several patients in the Wuhan district of China were diagnosed with ruthless pneumonia caused by an unknown virus. In response, an epidemiological alert was placed by the World Health Organization (WHO) on December 31, 2019.

By January 7, 2020, Chinese scientists had isolated the causative agent and named the virus as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In a few months that followed, the virus spread its cruelty across far-off countries resulting in the present-day infamous pandemic situation of the coronavirus disease 2019 (COVID-19). No doubt, it is one of the most desperate situations that the world has seen in recent times as many of the countries face a complete lockdown. About 80% of the patients remain asymptomatic being only the carrier of the disease and mostly remain undetected. So, the virus could infect more and more people while causing deaths of the more vulnerable ones. It has been observed that most susceptible ones are the old age people, the ones with the compromised immune system and pre-existing respiratory ailments, the new-borns and the expected mothers. It has also been found that the immune system of patients with SARS-CoV-2 infection gets drastically affected as the surviving T-cells are functionally exhausted, suggesting that, they are at potential risk of developing secondary infections that cannot occur if the immune system is strong and healthy. With a mortality rate of less than 7% the virus has already claimed 1.4 lakh lives worldwide and infected more than 20 lakhs within just five months of its outbreak recorded to date. But unfortunately, this is not the actual number, since the number of tests done to detect the disease is much less in most of the countries. Therefore, the actual number of the unlucky people infected with this RNA virus could be much larger and this points a serious concern.

No one in their wildest imagination could have ever thought that someday a mutant flu virus would cage them in their homes and make them go to banks and markets while dressing like a robber, such as the dramatic impact of the COVID-19. According to a recent study, it has been observed that air pollution could be an important issue in the enhanced severity of the infection. It has been proposed that prolonged exposure to air pollution could impair the first line of defense of upper airways, such individuals are at a higher risk of developing acute respiratory disease syndromes(ARDS). They are much more vulnerable to being invaded by the virus as it could easily surpass the already weakened upper respiratory defenses while reaching the lower airways. In that case, it would cause a heavy toll on the already weakened immune system and the effect could be fatal. Since the modification of the immune system had taken place through prolonged exposure to pollution therefore short term improvement in air quality would not improve the immune power of individuals. This might be the case of Lombardy and Emilia Romagna of northern Italy, which were the two most polluted areas of Europe. Despite, the drastic reduction in pollution the mortality rates due to infection has not quite lowered there. Perhaps the first lesson to counter the pandemic should be to lower the pollution and live in complete harmony with nature. Though nothing is proved yet, air pollution could be a cause that will increase the death rate of this particular infection.

        To combat this dire situation, our valiant battalions of scientists and doctors, have launched large scale research at the frontlines to quickly find out a remedy to the disease. Right now there is no available drug or vaccine that is present to fight against this deadly virus. So, repurposing of existing various drugs could be a successful alternative to counter the disease since the time is very short and the development of a particular vaccine would take a longer time.

Many compounds have been found to have a probable clinical advantage against the virus. Notable among them, are:

• Chloroquine and Hydroxychloroquineare the compounds that prevent the generation of inflammatory signals. Biochemically, it interferes with the interaction of the toll-like receptor(TLR)  and the mature virion and prevents the cytokine production.

• Oseltamivir is a neuraminidase inhibitor that is thought to disrupt the virus-host cell interaction. In India, it is already prescribed to patients suspected to have COVID-19 and are already displaying mild symptoms like low-grade fever, cough, malaise, rhinorrhea, sore throat without shortness of breath.

• Arbidol (Umifenovir) has shown a promising inhibitory effect in lowering the reproduction rate of the virus in vitro. Currently, this drug is under phase 4 clinical trial.

• Ribavirin prevents the replication of RNA virus by acting as a nucleoside analog and suppressing the activity of inosine monophosphate dehydrogenase which in turn downregulates the synthesis of guanosine triphosphate (GTP). Ribavirin had been widely used to treat SARS patients in Hong Kong. Thus, it could be a possible option for COVID-19 treatment.

• Ritonavir and Lopinavir have been found to bind to the proteinase 3CL-pro of the SARS-CoV-2 that cleaves the polyprotein at 11sites from the C-terminus and inhibits its function, thereby disrupting protein expression. Thus is a promising drug that could be used often in combination with other drugs.

• Darunavir and Cobicistat are HIV protease inhibitors. Currently under the phase 3 clinical trial.

• ASC09F is also an HIV inhibitor currently under phase 3 clinical trial in combination with Oseltamivir.

Remdesivirand Favipiravirare Inhibitors of RNA polymerase hence thought to be used against the SARS-CoV-2 which is an RNA virus.

Apart from these compounds, with the help of bioinformatics analysis, a compound namedBaricitinib has been identified to be helpful as it could inhibit the enzyme AP-2-associated protein kinase 1 (AAK1) that plays an important role in the cellular entry of the virus. Another compound camostat mesylate, that inhibits the enzyme TMPRSS2 that is involved in the maturation of the spike protein on the virion could also be helpful. By using the principles of RDT a soluble recombinant ACE2 protein has been designed that could competitively bind to the virus and prevent its binding to the membrane-anchored version of the receptor. This innovation has worked well in vitro and monkey models and could perhaps effectively combat the disease.  Antiviral therapy using the Interferon-alpha (IFNα) also looks promising as it could directly interfere with the viral replication and prevent its spread. Tocilizumab, an inhibitor of interleukin 6 is also reported to be useful in severe cases of COVID-19 with elevated IL-6.

Certain Chinese traditional medicine has also surfaced as a potential means to treat the pandemic and is consequently being investigated. Notable, among them, are:

• Glycyrrhizin, an active component of licorice roots that could competitively bind to ACE2 and also efficiently disrupted the replication of SARS-CoV-2 in-vitro.
• Baicalin, isolated from Scutellaria baicalensis the famous Chinese skullcap, is a flavone that has exhibited certain antiviral activity.
• Quercetin, another compound has been reported to exert antiviral activity by blocking host cell entry and disrupting the action of  the viral protienase 3CLpro.
• Hesperetin, a compound isolated from citrus fruits inhibits the cleavage activity of the 3C-like protease (3CLpro).

Apart, from these Chinese ‘nuskhas’, different immunotherapeutic approaches are also being taken. One of these is Convalescent plasma therapy, where the convalescent plasma of the recovered patient is used to treat the newly infected has been started.

Though we do not have any scientifically recommended remedy to this particular disease right now, there are many current possibilities to counter the virus and we can hope that the battle won’t last long for it is just a matter of time, when we would have our perfect remedy and then just like in every era we would emerge victorious in the race of the survival of the fittest.