Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused an outbreak in Wuhan city, China and quickly spread worldwide. Currently, there are no specific drugs or antibodies that claim to cure severe acute respiratory diseases. For SARS-CoV-2, the spike (S) protein recognizes and binds to the angiotensin converting enzyme 2 (ACE2) receptor, allowing viral RNA to enter the host cell. The main protease (Mpro) is involved in the proteolytic process for mature non-structural proteins, and RNA-dependent RNA polymerase (RdRp) is responsible for the viral genome replication and transcription processes. Owing to the pivotal physiological roles in viral invasion and replication, S protein, Mpro, RdRp are regarded as the main therapeutic targets for coronavirus disease 2019 (COVID-19). In this review, we carried out an evolutionary analysis of SARS-CoV-2 in comparison with other mammal-infecting coronaviruses that have sprung up in the past few decades and described the pathogenic mechanism of SARS-CoV-2. We displayed the structural details of S protein, Mpro, and RdRp, as well as their complex structures with different chemical inhibitors or antibodies. Structural comparisons showed that some neutralizing antibodies and small molecule inhibitors could inhibit S protein, Mpro, or RdRp. Moreover, we analyzed the structural differences between SARS-CoV-2 ancestral S protein and D614G mutant, which led to a second wave of infection during the recent pandemic. In this context, we outline the methods that might potentially help cure COVID-19 and provide a summary of effective chemical molecules and neutralizing antibodies.
【저자키워드】 Structure, Evolution, SARS-CoV-2, pathogenic mechanism, targeting inhibition, 【초록키워드】 COVID-19, coronavirus disease, severe acute respiratory syndrome coronavirus 2, neutralizing antibody, antibodies, Coronavirus disease 2019, ACE2, coronavirus, pandemic, S protein, Neutralizing antibodies, antibody, Infection, drug, protease, severe acute respiratory syndrome Coronavirus, respiratory diseases, angiotensin converting enzyme, non-structural proteins, Replication, MPro, Spread, China, Protein, Viral, outbreak, comparison, Wuhan, RdRP, RNA-dependent RNA polymerase, D614G, second wave, small molecule, Viral RNA, mutant, receptor, respiratory, inhibitor, mechanism, Small molecule inhibitors, Analysis, angiotensin, Invasion, physiological, therapeutic target, (RdRp, host cell, acute respiratory diseases, acute respiratory syndrome, acute respiratory syndrome coronavirus, enzyme, help, pathogenic, viral invasion, viral genome replication, transcription processes, effective, bind, complex structure, responsible, described, analyzed, caused, carried, involved, inhibit, in viral, recognize, proteolytic, small molecule inhibitor, 【제목키워드】 inhibition, origin, targeting,