<strong>Coronavirus ORF1ab Polyprotein Associated Nsp16 Protein is a RlmE Methyltransferase and May Methylate 21S Mitochondrial rRNA of Most Mells Inhibiting Protein Synthesis</strong>

Abstract

Covid-19 infections are rapidly spreading worldwide with more than 100000 death and thus understanding the molecular mechanism of tropism of human cells is an urgent need for drug design. We have described here a bioinformatics approach to predict the functional aspects of non-structural nsp16 protein of Corona virus. The covid-19 7098 AA large polyprotein was degraded into sixteen proteins and last nsp16 protein was found an RlmE type rRNA methyltransferase. Nsp16 has no similarity to bacterial RlmABCD but has 25 percent similarity to the bacterial RlmE protein which methylates the U2551 2-hydroxy group of Ribose. The nsp16 proteins of different corona viruses like covid-19, bat-coronavirus, SARS and MERS have strong homology. Mrm2 and Dim1 like yeast and mammalian rRNA methyltransferases have 26-33 percent homologies but not with 2-O-capping MTase as reported previously. Rrp8 MTases also has no similarity to nsp16. We postulated that mitochondrial rRNA methylation of bronchial cells were mediated by the nsp16 protein causing inhibition of protein synthesis due to poor assembly of aminoacyl-tRNA or mRNA and peptidyl transferase at the PTC. This is one of the new molecular mechanism of corona virus cellular tropism and different than ACE-2 mediated blockage of cellular signalling to inhibit aldesterone biosynthesis with abnormal Na+ ions in cells. We also designed primers based on nsp16 cDNA sequence (nt 20659-21552, accession no MT121215) specific for Covid-19 diagnosis by RT-PCR.

Multi-Alignment Comparison of Coronavirus Non-Structural Proteins Nsp13- Nsp16 with Ribosomal Proteins and other DNA/RNA Modifying Enzymes Suggested their Roles in the Regulation of Host Protein Synthesis

“…We searched the 200 different DNA/RNA modifying/binding enzymes from gene bank database to compare with Nsp13/14.15/16 of coronavirus OFR1ab-derived non-structural proteins and obtained very good information regarding the structure and functions of those proteins. Such analysis documented rarely and could not found in the NCBI PubMed database [1]. We also like to work on phytoantibiotics and nanocarrier-mediated toxic drug delivery and such technology may welcome for coronavirus therapy.…”

“…NCBI PubMed portal (www.ncbi.nlm.nih.gov/pubmed) used to retrieve references and papers. CLUSTAL Omega Phylogenetic tool used to determine the closer structural similarities among the proteins and Seq-2 BLAST was used to confirm percentage of sequence homology between two related proteins [1].…”

“…phosphorylation in patient leading to sudden death [1]. We also communicated that Coronavirus Nsp2 protein was a novel RNA Topoisomerase [2].…”

“…Roles of DIssE RNA gene rearrangement to make viral regulatory proteins of infectious RNA viruses seems complex but important molecular target. We will discuss the structural features of those enzymes and their interrelationship accelerating viral life cycle but at same time causing acute pathogenesis due to lysis of lung cells [1,8]. It claimed within 3 months 280000 lives worldwide and >3 million peoples suffered high fever, cough, low pressure and intensive care life for one month.…”

Hyper-Variable Spike Protein of Omicron Corona Virus and Its Differences with Alpha and Delta Variants: Prospects of RT-PCR and New Vaccine

“…Corona virus is a large positive-sense RNA virus with a compact 29,980 nucleotides-long genome and COVID-19 is related to six different corona viruses like CoV-229E, CoV-HKU1, CoV-OC43, CoV-NL63, SARS-CoV and Middle East respiratory syndrome corona virus (MERS-CoV) [1][2][3][4][5]. It has structural proteins (S, M, N, E) at the 3'end and 5' two very large poly-proteins (2/3 of the genome) which degraded into sixteen non-structural proteins (nsp1-16) including RNA-dependent RNA polymerase (nsp12) [6], two proteases (nsp3 and nsp5) [7,8], RNA topoisomerase (nsp2) [9], RNA helicase (nsp13) [10], nucleases (nsp15) [11] and methyl transferases (nsp16) [12] (figure 1A). Spike protein (1273 aa) is a trimeric class 1 transmembrane glycoprotein and its RBD domain (335-515 aa) acts as receptor binding domain to bind ACE-2 receptor of host cells for virus entry [13] (figure 1B).…”