Molecular mechanisms and pharmacological interventions in the replication cycle of human coronaviruses

Fernando Simabuco; Rodrigo  Tamura; Isadora Carolina Betim Pavan; Mirian  Morale; Armando  Ventura

doi:10.1590/SciELOPreprints.1045

article.authors6a0b8d5f6eeb5

Fernando Simabuco University of Campinas https://orcid.org/0000-0002-1672-9686
Rodrigo Tamura Universidade Federal de São Paulo (UNIFESP)
Isadora Carolina Betim Pavan Faculdade de Ciências Farmacêuticas (FCF), Universidade Estadual de Campinas (Unicamp)
Mirian Morale Centro de Oncologia Translacional, Instituto do Câncer do Estado de São Paulo (ICESP), Departamento de Radiologia e Oncologia, Faculdade de Medicina, Universidade de São Paulo (USP)
Armando Ventura Instituto de Ciências Biomédicas (ICB), Universidade de São Paulo (USP)

DOI:

https://doi.org/10.1590/SciELOPreprints.1045

Palavras-chave:

coronavirus, SARS-CoV-2, COVID-19, viral replication, RNA virus

Resumo

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), as well as SARS-CoV from 2003 and MERS-CoV from 2012, is a member of the Betacoronavirus genus of the Nidovirales order and is currently the cause of the pandemic called COVID-19 (or Coronavirus disease 2019). COVID-19 is characterized by cough, fever, fatigue, and severe cases of pneumonia and has affected more than 9.1 million people worldwide until June 22^nd, 2020. Here we present a review of the cellular mechanisms associated with human coronaviruses replication, including the unique molecular events related to the replication transcription complex (RTC) of coronaviruses. Information regarding the interactions between each viral protein and cellular proteins is presented, associating to known host-pathogen implications for the coronavirus biology. Finally, a specific topic addresses the current attempts for pharmacological interventions against COVID-19, highlighting the possible effects of each drug on the molecular events of viral replication. This review intends to contribute to future studies for a better understanding of the SARS-CoV-2 replication cycle and the development of pharmacological approaches targeting COVID-19.