Potential Small-molecule Drug Targets for COVID-19

Diagnostics

Viruses must enter the host cell to replicate in order to function. Therefore, antiviral drugs can be designed for a series of targets in the process of virus interaction with cell receptors, gene replication, transcription and translation when the virus invades host cells and completes its life cycle. Chemical Small-molecule targeted drugs are one of the types of drugs currently expected to be used for the treatment of COVID-19. There are now several small molecule drugs in clinical trials, and their effectiveness and safety against SARS-CoV-2 need to be further verified.

1. Protease inhibitor

The anti-viral drug Lopinavir/Ritonavir developed for HIV can effectively inhibit the important role of proteases in the replication and function of the virus, thereby interfering with the assembly process of the virus to make it non-infectious and ultimately prevent virus infection. Low-dose ritonavir can inhibit the liver’s catabolism of lopinavir, and achieve the effect of improving the bioavailability of lopinavir. Therefore, the combined use of two protease inhibitors can effectively improve the antiviral treatment effect. The protease activity of HIV is similar to that of SARS-CoV-2, but the target structure is different. Therefore, whether this drug is really effective against the SARS-CoV-2 still needs to pass rigorous clinical verification and must be used with caution.

2. RNA-dependent RNA polymerase (RdRP) inhibitor

Remdesivir (GS-5734) is a nucleoside analog developed by Gilead, a broad-spectrum antiviral drug. The drug was used in clinical trials against Ebola virus infection, but the results were not satisfactory. Remdesivir acts on RdRP and achieves antiviral effects by inhibiting viral RNA replication. Previous studies have confirmed that Remdesivir has certain effectiveness against SARS and MERS. Based on the similarity of the catalytic site structure of the SARS-CoV-2 and that of the SARS and MERS, it can be speculated that the target of the drug against the SARS-CoV-2 may be also equally effective.

Another kind of RdRP inhibitor, Favipiravir, is a class of broad-spectrum antiviral drugs that has been marketed and has a good therapeutic effect on severe influenza and drug-resistant patients, and can also effectively prevent the replication of the virus in the host cell. It is currently under clinical research for the SARS-CoV-2.

3. Antiviral drugs targeting the host

In addition to the above two drugs, there is a class of small molecule drugs that can regulate the interaction between the SARS-CoV-2 and the host by targeting the host and effectively inhibit the virus from invading human cells, which may also have certain therapeutic potential. These include chloroquine, an antimalarial drug that has been used clinically for more than 70 years, hydroxychloroquine, used in the treatment of autoimmune diseases, and Abidor developed for influenza viruses. These drugs are aimed at the targets of viruses invading human cells and cell fusion.

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