Viewing SARS-CoV-2 Nucleocapsid Protein in Terms of Molecular Flexibility

Abstract

The latest coronavirus SARS-CoV-2, which causes coronavirus disease 2019 (COVID-19) pneumonia leading to the pandemic, contains 29 proteins. Among them, nucleocapsid protein (NCoV2) is one of the abundant proteins and shows multiple functions including packaging the RNA genome during the infection cycle. It has also emerged as a potential drug target. In this review, the current status of the research of NCoV2 is described in terms of molecular structure and dynamics. NCoV2 consists of two domains, i.e., the N-terminal domain (NTD) and the C-terminal domain (CTD) with a disordered region between them. Recent simulation studies have identified several potential drugs that can bind to NTD or CTD with high affinity. Moreover, it was shown that the degree of flexibility in the disordered region has a large effect on drug binding rate, suggesting the importance of molecular flexibility for the NCoV2 function. Molecular flexibility has also been shown to be integral to the formation of droplets, where NCoV2, RNA and/or other viral proteins gather through liquid-liquid phase separation and considered important for viral replication. Finally, as one of the future research directions, a strategy for obtaining the structural and dynamical information on the proteins contained in droplets is presented.

Interactome Analysis of the Nucleocapsid Protein of SARS-CoV-2 Virus

“…Recent studies have pointed out that the SARS-CoV-2 N protein is capable of forming or regulating biomolecular condensates by interacting with RNA and key host cell proteins [ 47 , 48 ]. These structures are considered to play important roles in viral replication and assembly [ 49 ]. Thus, we compared our dataset with recently reported SARS-CoV-2-induced RNA-binding proteome and host transcriptional response datasets, and many proteins overlapped with these two datasets.…”

Reliable Diagnostics of SARS-CoV-2 Infections Using One- and Two-Gene Molecular Tests for a Viral RNA Detection—Results Questioning Previous Observations

“…However, the use of the latter can reduce the rate of false-negative results [20,21]. This diagnostic approach increases the probability of viral genetic material detection, including, for example, the sequences with genes mutations [37,38]. Currently, this is particularly important due to the observed dynamically increasing number of new SARS-CoV-2 variants [22,23].…”

Structural biology of SARS-CoV-2: open the door for novel therapies

“… 92 In the future, this antibody could be modified in a site-directed manner based on specific structural information to allow the production of more efficient and broader spectrum monoclonal antibodies. In addition to antibodies, some small molecules (such as rapamycin 93 and PJ34 94 ) that interfere with the RNA binding of N-NTD and dimerization of N-CTD have also been recommended as inhibitors of the N protein.…”