Available antiviral options against SARS-COV-2 replication

  • by VaccineHealthCenter

The Covid-19 pandemic is caused by a novel coronavirus strain SARS-Cov-2. To date, no specific drug has been identified to treat the pandemic. This owes to the fact that developing a drug takes years of research. Consequently, there is a need to take advantage of the repurposing broad-spectrum existing antiviral drugs and use them to work against SARS-CoV-2 replication. Covid-19 pandemic is an international concern as its scope is not limited to specific countries. Instead, the disease knows no boundaries and affects the young and old, male and female, rich or poor, and the natives and foreigners.

Pathogenesis and the life cycle of coronavirus

In determining which ones of the broad-spectrum antiviral drugs can be used to control SARS-CoV-2 replication, it is crucial to take a deep study of the coronavirus and identify the features in its life cycle and pathogenesis that make it a dangerous virus. In the structure of the coronavirus, we find the following features which promote the virus’ pathogenesis;

  • The piece of virus spike protein (S Protein)
  • RNA-dependent RNA polymerase (RdRp)
  • 3-chymotrypsin-like protease (3CLpro)
  • The papain-like protease (PLpro)

By targeting these features in the pathogenesis and the life cycle of the coronavirus, the available antiviral drugs with high efficacy to prohibiting virus replication can form the basis for alternative treatment options for SARS-CoV-2 in Covid-19 patients.

Existing antiviral drugs options for SARS-CoV-2 alternative treatment

Viruses are not a new thing. They have been there since time immemorial. Even the infectious SARS-CoV-2 is the seventh strain of the coronavirus, after HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, MERS-CoV. Since the viruses have been around, it means that there are antiviral drugs that have always been used to manage them by downsizing the virus replication. Here are some of the existing antiviral drugs doctors can use of Covid-19 patients to stagnate SARS-CoV-2 replication;
SARS-CoV-2 cell entry limiting antivirals

  • Griffithsin- this is an algae-derived lectin with a broad-spectrum antiviral activity targeting viral entry inhibition. In vivo and in vitro studies established that griffithsin’s identical carbohydrate domains can attach to the SARS-CoV spike glycoprotein, and inhibit the virus’ entry into the cells.
  • Nafamostat- although this drug is primarily used to treat acute pancreatitis, it has been shown to control the activity of MERS-CoV by inhibiting the host protease TMPRSS2, which the virus needs to prime and cause a virus infusion entry into the host cells. Because SARS-CoV-2 is another strain of coronavirus like MERS-CoV, a recent study suggests that nafamostat could be used in Covid-19 patients as an alternative treatment option because of its potential efficacy to inhibit the membrane fusion of SARS-CoV-2 with host cells.

SARS-CoV-2 protease-targeting antiviral drugs

  • Disulfiram- this is an antiviral drug used as a supportive treatment for chronic alcoholism and it works by inhibiting acetaldehyde dehydrogenase. The drug has also been studied and established for cancer treatment and latent HIV infection treatment. 2018 studies suggested that disulfiram could be used as a competitive inhibitor of SARS-CoV as well as an allosteric inhibitor of MERS-CoV PLpro, although there is insufficient clinical data to support this. Therefore, disulfiram can be used to inhibit the viral polyprotein cleavage by targeting the ZN bonds present in PLpro, NSP10, and NSP13 of SARS and SARS-CoV-2. These are features in SARS-CoV-2 that can be targeted to limit the virus's replication.
  • Lopinavir- this antiviral drug has been used wildly to treat HIV infection by inhibiting the viral protease together with ritonavir, an approved antiretroviral drug from the protease inhibitor class, is widely used as a booster for other protease inhibitor drugs. Lopinavir and ritonavir (Kaletra) were established to possess a high affinity for the pocket site of the 3CLpro enzyme in SARS-CoV and SARS-CoV-2 and may act as an inhibitor for viral replication. However, the efficacy in human beings has not been ascertained as the trials were done in vitro and on animals.

Inhibiting SARS-CoV-2 by targeting RNA-dependent RNA polymerase
The vital enzyme RdRp can be targeted and used for SARS-CoV-2 replication inhibition. Here are some drugs that target this feature;

  • Favipiravir (Avigan, T-705)- this guanine analog and pyrazinecarboxamide derivative has a unique activity against many RNA viruses such as influenza viruses, yellow fever virus, arenaviruses, and enteroviruses. Additionally, Favipiravir can selectively inhibit the viral RdRp without inhibition of RNA or DNA synthesis in mammalian cells, meaning that when subjected to further tests and human trials, it could be used to limit SARS-CoV-2 replication.
  • Ribavirin- this is a guanosine analog that has been approved and used to treat HCV and respiratory syncytial virus (RSV). Through the induction of several mutations in the genome of the RNA viruses targeting the viral RdRp, the drug can block viral RNA synthesis through viral mRNA-capping termination. Clinical data on the drug's efficacy, when used in human Covid-19 patients, is still unknown, calling for further studies.
  • Other drugs- there are lots of antiviral drugs in this category that upon thorough research, could be found to be substantial inhibitors of the SARS-CoV-2 replication. Such include Remdesivir, Galidisivir, and many more.

Although a cure for the Covid-19 pandemic has not been found (if ever found, a lot of time will be needed to research), several existing repurposing antivirals can substantially treat the disease by targeting features in SARS-CoV-2 pathogenesis and life cycles. This article looked at such antiviral drugs.