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The main protease of SARS-CoV-2 as therapeutic target to development specific drugs to treat COVID-19


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Abstract

The pandemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) denominated COVID-19 is an important problem of world public health because do not have specific drugs and vaccines available to control the disease progression and the rapid virusspreading. SARS-CoV-2 genome resemble to other SARS-CoV andMERS- COVcoronaviruses genomes, thus drugs developed for SARS and MERS treatment may be used for COVID-19. The aim of this work is discuss the molecular target of SARS- CoV-2, the main protease, a chymotrypsin-like named as 3CLpro, for a rational devolpment of specific molecules anti-SARS-CoV-2 with broad-spectrum anti-coronavirus activities. This study is a literature mini review using 47 articles obtained from Public Medline and Science directmainly from this year 2020. The coronaviruses infection is mediated by spike protein from viral capsid which bind to ACE2 receptor in the host cells which endocytes the viruses RNA, which is translated to proteins that are cleavead by proteases, mainly the 3CLpro. This enzyme is crucial to SARS-CoV-2 replication and its inhibition can prevent the virus replication. Thus, it is an important coronaviruses target because the amino acid sequence of 3CLpros from SARS, MERS and SARS-CoV-2 have high similarity. In silico studies have been demonstrated that synthetic small molecules, natural products, peptidomimetic inhibitors, and HIV inhibitors had different docking scores with SARS- CoV-23CLpro. However, peptidomimetic inhibitors seems to be better inhibitors to this protease and promise dugs to treat COVID-19 and other diseases caused by coronaviruses. 

Keywords

SARS-CoV-2, Covid-19, therapeuctic target, 3CLproMain protease, inhibitors

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