Characterization of SARS-CoV-2 isolated from a patient in Iran compared to SARS-CoV-2 different variants.

Since the onset of the global epidemic of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), whole genome sequencing of virus in all countries has been considered to track and predict virus transmission and variation patterns. In the current study we reported a novel complete genome sequence of SARS-CoV-2 isolated from Iran. Genomics variations and protein sequences were evaluated for the isolated sequence and seven Iranian complete genome sequences of SARS-CoV-2 from NCBI using the reference genome of the SARS-CoV-2 Wuhan-Hu-1. The results showed six nucleotide substitutions. The multiple sequence alignment of the spike protein of the Wuhan-Hu-1 strain and the emerging variants indicated similar its residue pattern in the current sequence to the Wuhan-Hu-1 strain. There were relatively similar binding affinity and residues involved in the interactions of the spike receptor-binding domain (RBD) of the Wuhan-Hu-1 strain, the variants and Hormozgan With angiotensin-converting enzyme 2 (ACE2). Tracing the phylogeny of virus indicated distinct clustering of Iranian variants in branches close to the Asian countries. The mutation effect study on the function of proteins predicted neutral impact of all six nucleotide substitutions. However, the free energy calculations indicated a decreasing the protein stability related to the mutations. This data, consistent with similar studies, showed that despite the high similarity in the nucleotide sequence of the SARS-CoV-2, the mutation pattern varies from country to country. Therefore, any country can benefit from these studies to track and find appropriate strategies for treating and controlling the epidemic.Communicated by Ramaswamy H. Sarma.

Different compounds against Angiotensin-Converting Enzyme 2 (ACE2) receptor potentially containing the infectivity of SARS-CoV-2: an in silico study.

Novel SARS coronavirus or SARS-CoV-2 is a novel coronavirus that was identified and spread from Wuhan in 2019. On January 30th, the World Health Organization declared the coronavirus outbreak as a Global Public Health Emergency. Although Remdesivir and Molnupiravir are FDA-approved drugs for COVID-19, finding new efficient and low-cost antiviral drugs against COVID-19 for applying in more countries can still be helpful. One of the potential sources for finding new and low-cost drugs is the herbal compounds in addition to repurposing FDA-approved drugs. So, in this study, we focused on finding effective drug candidates against COVID-19 based on the computational approaches. As ACE2 serves as a critical receptor for cell entry of this virus. Inhibiting the binding site of SARS-CoV-2 on human ACE2 provides a promising therapeutic approach for developing drugs against SARS-CoV-2. Herein, we applied a bioinformatics approach to identify possible potential inhibitors of SARS-CoV-2. A library of FDA-approved compounds and five natural compounds was screened using Smina docking. Top-docking compounds are then applied in Molecular Dynamics (MD) simulation to assess the stability of ACE2-inhibitor complexes. Results indicate that Luteolin and Chrysin represent high conformation stability with ACE2 during 120 ns of Molecular Dynamics simulation. The binding free energies of Luteolin and Chrysin were calculated by the Molecular Mechanics/Poisson-Boltzmann Surface Area method (MM/PBSA) which confirmed the relative binding free energy of these drugs to ACE2 in favor of the effective binding. So, Luteolin and Chrysin could sufficiently interact with ACE2 and block the Spike binding pocket of ACE2 and can be a potential inhibitor against the binding of SARS-CoV-2 to ACE2 receptor which is an early stage of infection. Luteolin and Chrysin could be suggestive as beneficial compounds for preventing or reducing SARS-CoV-2 transmission and infection which need experimental work to prove.

Active site-based analysis of structural proteins for drug targets in different human Coronaviruses.

Seven types of Coronaviruses (CoVs) have been identified that can cause infection in humans, including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, SARS-CoV, HCoV-MERS, and SARS-CoV-2. In this study, we investigated the genetic structure, the homology of the structural protein sequences, as well as the investigation of the active site of structural proteins. The active site of structural proteins was determined based on the previous studies, and the homology of their amino acid sequences and structure was compared. Multiple sequence alignment of Spike protein of HCoVs showed that the receptor-binding domain of SARS-CoV-2, SARS-CoV, and MERS-CoV was located at a similar site to the S1 subunit. The binding motif of PDZ (postsynaptic density-95/disks large/zona occludens-1) of the envelope protein, was conserved in SARS-CoV and SARS-CoV-2 according to multiple sequence alignment but showed different changes in the other HCoVs. Overall, spike protein showed the most variation in its active sites, but the other structural proteins were highly conserved. In this study, for the first time, the active site of all structural proteins of HCoVs as a drug target was investigated. The binding site of these proteins can be suitable targets for drugs or vaccines among HCoVs.

Structure-based study of immune receptors as eligible binding targets of coronavirus SARS-CoV-2 spike protein.

One of the most important challenges in the battle against contagious SARS-CoV-2 is subtle identification of the virus pathogenesis. The broad range of COVID-19 clinical manifestations may indicate diversity of virus-host cells. Amongst key manifestations, especially in severe COVID-19 patients, reduction and/or exhaustion of lymphocytes, monocytes, basophils, and dendritic cells are seen.; therefore, it is required to recognize that how the virus infects the cells. Interestingly, angiotensin-converting enzyme 2 (ACE2) as the well-known receptor of SARS-CoV-2 is low or non-expressed in these cells. Using computational approach, several receptor candidates including leukocyte surface molecules and chemokine receptors that expressed in most lineages of immune cells were evaluated as the feasible receptor of spike receptor-binding domain (RBD) of SARS-CoV-2. The results revealed the higher binding affinity of CD26, CD2, CD56, CD7, CCR9, CD150, CD4, CD50, XCR1 and CD106 compared to ACE2. However, the modes of binding and amino acids involved in the interactions with the RBD domain of spike were various. Overall, the affinity of immune receptor candidates in binding to SARS-CoV-2 RBD may offer insight into the recognition of novel therapeutic targets in association with COVID-19.