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

Author(s)

Simabuco, Fernando Moreira ; Tamura, Rodrigo Esaki ; Betim Pavan, Isadora Carolina ; Morale, Mirian Galliote ; Ventura, Armando Morais

• Document type: Journal article
• Source: GENETICS AND MOLECULAR BIOLOGY; v. 44, n. 1, p. 18-pg., 2021-01-01.

Abstract

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), as well as SARS-CoV from 2003 along with 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, which is characterized by cough, fever, fatigue, and severe cases of pneumonia, has affected more than 23 million people worldwide until August 25th, 2020. Here, we present a review of the cellular mechanisms associated with human coronavirus replication, including the unique molecular events related to the replication transcription complex (RTC) of coronaviruses. We also present information regarding the interactions between each viral protein and cellular proteins associated 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 aid future studies for a better understanding of the SARS-CoV-2 replication cycle and the development of pharmacological approaches targeting COVID-19. (AU)

• FAPESP's process: 16/25139-0 - Proteins related to Toll Like Receptors signaling on HPV tumorigenesis
• Grantee: Mirian Galliote Morale
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/15619-2 - Development of high capacity adenoviral system expressing antitumoral genes
• Grantee: Rodrigo Esaki Tamura
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 18/14818-9 - Study of molecular targets important for the control of cancer metabolism: the mTOR/S6K pathway as a central role
• Grantee: Fernando Moreira Simabuco
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 20/05346-6 - Interaction studies between cellular proteins and viral proteins of the new coronavirus 2019 (SARS-CoV-2)
• Grantee: Fernando Moreira Simabuco
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/08391-2 - Functional and molecular studies of the human protein kinase Nek6 as a target candidate for drug design in Prostate Cancer
• Grantee: Isadora Carolina Betim Pavan
• Support Opportunities: Scholarships in Brazil - Doctorate