The pneumonia outbreak caused by Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) infection poses a serious threat to people worldwide. Although vaccines have been developed, antiviral drugs are still needed to combat SARS-CoV-2 infection due to the high mutability of the virus. SARS-CoV-2 main protein (M ) is a special cysteine protease that is a key enzyme for SARS-CoV-2 replication. It is encoded by peptides and is responsible for processing peptides into functional proteins, making it an important drug target. The paper reviews the structure and peptide-like inhibitors of SARS-CoV-2 M , also the binding mode and structure-activity relationship between the inhibitors and M are introduced in detail. It is hoped that this review can provide ideas and help for the development of anti-coronavirus drugs such as COVID-19, and help to develop broad-spectrum antiviral drug for the treatment of coronavirus diseases as soon as possible.
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