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

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 25 th , 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.

Outcome and death risk of diabetes patients with Covid-19 receiving pre-hospital and in-hospital metformin therapies

“…Chloroquine was proposed as an early repurposing drug against SARS-CoV-2, in vitro it has shown activity against MERS-CoV and SARS-CoV [ 1 ]. Analysis of the Cochrane Central Register of Controlled Trials (CENTRAL) indicated that use of chloroquine/hydroxychloroquine has little or no effect on the risk of death, showing increase in adverse events and having no protective effect [ 29 ].…”

“…The COVID-19 pandemic is caused by SARS-CoV-2, a member of the Betacoronavirus genus of the Nidovirales order, its single stranded positive polarity RNA encodes non-structural and structural proteins, one important structural protein is the Spike, which mediates recognition of the ACE2 cell receptor. The non-structural proteins play pivotal role in cell regulation, that impacts host response to viral infection [ 1 ]. Data from the World Health Organization (WHO) points to over 178 million confirmed cases and 3,864,180 deaths until June, 21st 2021 ( https://covid19.who.int/ ).…”

Increased mTOR signaling, impaired autophagic flux and cell-to-cell viral transmission are hallmarks of SARS-CoV-2 infection

“…The results suggest that high mTOR signaling and compromised autophagy flux could be a cell response to the viral infection or pre-existing conditions that could contribute to the poor prognosis of the disease. In addition to blocking autophagy flux, high mTOR activity could favor capdependent translation of SARS-CoV-2 genomic and 3'-co-lateral capped subgenomic mRNAs [42][43][44][45].…”

Effects of Human Nucleolus Upon Guest Viral-Life, Focusing in COVID-19 Infection: A Mini- Review

“…This pandemic now has been re-named as SARS-CoV-2 by the International Committee of Taxonomy of Viruses (20). Entering the host cell, the main target of invader viruses is to disorganize protein synthesis, including altering nucleolar proteome machinery for their replication (22)(23)(24)(25)(26).…”