Structural and Drug Screening Analysis of the Non-structural Proteins of Severe Acute Respiratory Syndrome Coronavirus 2 Virus Extracted From Indian Coronavirus Disease 2019 Patients

Abstract

The novel coronavirus 2 (nCoV2) outbreaks took place in December 2019 in Wuhan City, Hubei Province, China. It continued to spread worldwide in an unprecedented manner, bringing the whole world to a lockdown and causing severe loss of life and economic stability. The coronavirus disease 2019 (COVID-19) pandemic has also affected India, infecting more than 10 million till 31st December 2020 and resulting in more than a hundred thousand deaths. In the absence of an effective vaccine, it is imperative to understand the phenotypic outcome of the genetic variants and subsequently the mode of action of its proteins with respect to human proteins and other bio-molecules. Availability of a large number of genomic and mutational data extracted from the nCoV2 virus infecting Indian patients in a public repository provided an opportunity to understand and analyze the specific variations of the virus in India and their impact in broader perspectives. Non-structural proteins (NSPs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus play a major role in its survival as well as virulence power. Here, we provide a detailed overview of the SARS-CoV2 NSPs including primary and secondary structural information, mutational frequency of the Indian and Wuhan variants, phylogenetic profiles, three-dimensional (3D) structural perspectives using homology modeling and molecular dynamics analyses for wild-type and selected variants, host-interactome analysis and viral–host protein complexes, and in silico drug screening with known antivirals and other drugs against the SARS-CoV2 NSPs isolated from the variants found within Indian patients across various regions of the country. All this information is categorized in the form of a database named, Database of NSPs of India specific Novel Coronavirus (DbNSP InC), which is freely available at http://www.hpppi.iicb.res.in/covid19/index.php.

Emerging Mutations in Nsp1 of SARS-CoV-2 and Their Effect on the Structural Stability

“…Moreover, mutations in Nsp1 prevent its release from the nascent polyprotein ORF1a, limiting the viability of the virus. The Nsps are important for vaccine development and as potential drug targets [ 32 , 33 ] because of their role in viral genome replication, disrupting the host cell environment, and interfering with the immune system and signaling [ 34 , 35 ]. SARS-CoV-2 is evolving rapidly and genetic diversity seems to accumulate in a short duration.…”

SARS-CoV-2 Mutations and Their Impact on Diagnostics, Therapeutics and Vaccines

“…Mohammad et al ( 58 ) further speculate T190I and A191V in 3CLpro can alter polarity and affect the binding of therapeutic molecules. Moreover, several geographical studies have been published, where Indian samples reveal a high mutation frequency in nsp2, nsp3, nsp4, nsp5, nsp6, nsp12, nsp14, and nsp16 ( 59 ). Whereas Wang et al ( 57 ) report frequent mutations in nsp2 and nsp13 in the US.…”

SARS-CoV-2 NSP-12 mutations survey during the pandemic in the world

“…A previous study demonstrated that this mutation has a negative impact on the packaging of the NSP-12 29 . This mutation was mainly detected in the mild and asymptomatic samples 34 .…”