Candidate drugs against SARS-CoV-2 and COVID-19.

Outbreak and pandemic of coronavirus SARS-CoV-2 in 2019/2020 will challenge global health for the future. Because a vaccine against the virus will not be available in the near future, we herein try to offer a pharmacological strategy to combat the virus. There exists a number of candidate drugs that may inhibit infection with and replication of SARS-CoV-2. Such drugs comprise inhibitors of TMPRSS2 serine protease and inhibitors of angiotensin-converting enzyme 2 (ACE2). Blockade of ACE2, the host cell receptor for the S protein of SARS-CoV-2 and inhibition of TMPRSS2, which is required for S protein priming may prevent cell entry of SARS-CoV-2. Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may limit spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic.

Structural features of coronavirus SARS-CoV-2 spike protein: Targets for vaccination.

Various human pathogenic viruses employ envelope glycoproteins for host cell receptor recognition and binding, membrane fusion and viral entry. The spike (S) glycoprotein of betacoronavirus SARS-CoV-2 is a homotrimeric class I fusion protein that exists in a metastable conformation for cleavage by host cell proteases furin and TMPRSS2, thereby undergoing substantial structural rearrangement for ACE2 host cell receptor binding and subsequent viral entry by membrane fusion. The S protein is densely decorated with N-linked glycans protruding from the trimer surface that affect S protein folding, processing by host cell proteases and the elicitation of humoral immune response. Deep insight into the sophisticated structure of SARS-CoV-2 S protein may provide a blueprint for vaccination strategies, as reviewed herein.