Novel Coronavirus Polymerase and Nucleotidyl-Transferase Structures: Potential to Target New Outbreaks.
J Phys Chem Lett
; 11(11): 4430-4435, 2020 Jun 04.
Article
in English
| MEDLINE | ID: covidwho-233085
ABSTRACT
The pandemic outbreak of a new coronavirus (CoV), SARS-CoV-2, has captured the world's attention, demonstrating that CoVs represent a continuous global threat. As this is a highly contagious virus, it is imperative to understand RNA-dependent-RNA-polymerase (RdRp), the key component in virus replication. Although the SARS-CoV-2 genome shares 80% sequence identity with severe acute respiratory syndrome SARS-CoV, their RdRps and nucleotidyl-transferases (NiRAN) share 98.1% and 93.2% identity, respectively. Sequence alignment of six coronaviruses demonstrated higher identity among their RdRps (60.9%-98.1%) and lower identity among their Spike proteins (27%-77%). Thus, a 3D structural model of RdRp, NiRAN, non-structural protein 7 (nsp7), and nsp8 of SARS-CoV-2 was generated by modeling starting from the SARS counterpart structures. Furthermore, we demonstrate the binding poses of three viral RdRp inhibitors (Galidesivir, Favipiravir, and Penciclovir), which were recently reported to have clinical significance for SARS-CoV-2. The network of interactions established by these drug molecules affirms their efficacy to inhibit viral RNA replication and provides an insight into their structure-based rational optimization for SARS-CoV-2 inhibition.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
RNA-Dependent RNA Polymerase
/
Betacoronavirus
/
Nucleotidyltransferases
Type of study:
Observational study
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
J Phys Chem Lett
Year:
2020
Document Type:
Article
Affiliation country:
Acs.jpclett.0c00571
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