Current state-of-the-art and potential future therapeutic drugs against COVID-19

Abstract

The novel coronavirus disease (COVID-19) continues to endanger human health, and its therapeutic drugs are under intensive research and development. Identifying the efficacy and toxicity of drugs in animal models is helpful for further screening of effective medications, which is also a prerequisite for drugs to enter clinical trials. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invades host cells mainly by the S protein on its surface. After the SARS-CoV-2 RNA genome is injected into the cells, M protein will help assemble and release new viruses. RdRp is crucial for virus replication, assembly, and release of new virus particles. This review analyzes and discusses 26 anti-SARS-CoV-2 drugs based on their mechanism of action, effectiveness and safety in different animal models. We propose five drugs to be the most promising to enter the next stage of clinical trial research, thus providing a reference for future drug development.

Keywords: animal model; anti-SARS-CoV-2 drug; screening; viral load; viral titer.

FIGURE 1

The mechanisms of SARS-CoV-2 entry into cells and the action mechanisms of COVID-19 therapeutic agents. There are two ways for SARS-CoV-2 to enter the cells. Left: SARS-CoV-2 was introduced by Cathepsins L if the TMPRSS2 is insufficient or a SARS-CoV-2–ACE2 complex does not encounter TMPRSS2; Right: TMPRSS2 is present, and the SARS-COV-2-ACE2 complex binds to the cell. Subsequently, the viral genome was then released by membrane fusion and replicated in the cells under the action of 3CL pro, PL pro, RdRp, and other enzymes. The red font represents anti-SARS-CoV-2 drugs that inhibit the corresponding targets.

FIGURE 2

The chemical structure of some anti-SARS-CoV-2 drugs. Note: The structure shown in the figure is the corresponding medicinal chemistry structure, the upper left corner is the drug name, and the italics are the drug classification.