COVID-19 Mutations: University Of Hawaii Scientists Warns P681H Mutation Emerging On Sequencings Of Many Globally Prevalent SARS-CoV-2 Strains
: Researchers the Department of Tropical Medicine, Medical Microbiology, and Pharmacology, John A. Burns School of Medicine- University of Hawaii have in a new study found that the P681H mutation emerging on sequencings of many globally prevalent SARS-CoV-2 strains.
This P681H mutation is immediately adjacent to the furin cleavage site, a known location of biological significance. It is said to affect an essential mechanism in the process of entry of the virus in the cell and hence could enhance binding capability and help in making the SARS-CoV-2 more infectious and contributing to its faster spread.
The COVID-19 pandemic has wreaked havoc around the world, caused over 1.94 million deaths and infected almost 90.2 million individuals along with affecting the global economy. Hawaii is not spared from the transmission of SARS-CoV-2 in the local population, including high infection rates in racial and ethnic minorities.
Early in the pandemic, the study team described various technologies used for the detection of SARS-CoV-2. Herein they characterize a 969-bp SARS-CoV-2 segment of the S gene downstream of the receptor-binding domain.
At the John A. Burns School of Medicine Biocontainment Facility, RNA was extracted from an oropharyngeal swab and a nasal swab from two patients from Hawaii who were infected with the SARS-CoV-2 in August 2020. Following PCR, the two viral strains were sequenced using Sanger sequencing, and phylogenetic trees were generated using MEGAX. Phylogenetic tree results indicate that the virus has been introduced to Hawaii from multiple sources.
Further, the study team decoded 13 single nucleotide polymorphisms across 13 unique SARS-CoV-2 genomes within this region of the S gene, with one non-synonymous mutation (P681H) found in the two Hawaii strains. The P681H mutation has unique and emerging characteristics with a significant exponential increase in worldwide frequency when compared to the plateauing of the now universal D614G mutation.
The P681H mutation is also characteristic of the new SARS-CoV-2 variants from the United Kingdom and Nigeria. Additionally, several mutations resulting in cysteine residues were detected, potentially resulting in disruption of the disulfide bridges in and around the receptor-binding domain. Targeted sequence characterization is warranted to determine the origin of multiple introductions of SARS-CoV-2 circulating in Hawaii.
Their study findings were published on a preprint server and are currently being peer reviewed. https://www.biorxiv.org/content/10.1101/2021.01.06.425497v1
The study team researchers showed that the S gene of the SARS-CoV-2 is continuously mutating according to the sequence and phylogenetic analysis. At the same time, a unique strain with an emerging mutation in an altered spike glycoprotein may be present in Hawaii.
Interestingly over the past year, there was a notable evolution of SARS-CoV-2 around the globe, which will continue to pose a serious threat. As of January 2021, four novel viral variants have been reported from the United Kingdom (VOC 202012/01/B.1.1.7), South Africa (501Y.V2), Nigeria (B.1.207), and Denmark (Mink Cluster V).
It must be noted that such a fast and constant pace of evolutionary changes affects the pathogenicity of SARS-CoV-2, a causative agent of coronavirus disease (COVID-19), and definitely warrants additional studies. In other words, an in-depth look at the genome is necessary to appraise all genomic alterations and adaptations.
To date it is already known that mutations in the viral spike glycoprotein can modify binding efficiency and, in turn, viral fitness. In fact, certain nucleotide mutations in the S gene of the SARS-CoV-2 can change its pathogenicity and diminish virulence, which is the reason why they have become pervasive in tracking the spread of the virus.
The study team from the University of Hawaii led by Dr David P. Maison, report the analysis of a 969-bp SARS-CoV-2 S gene from two patients from Hawaii in order to appreciate changes in the spike glycoprotein, which is also a prime target used by vaccines.
It was reported that at the John A. Burns School of Medicine Biocontainment Facility of the University of Hawaii, ribonucleic acid (RNA) was extracted from a nasal swab and an oropharyngeal swab from two male patients (mean age of 29.5 years) infected with the SARS-CoV-2 in August 2020.
Upon pursuing polymerase chain reaction (PCR), the two viral strains were sequenced with the use of Sanger sequencing (also known as the "chain termination method"). The latter was conducted on the amplicons by utilizing four primers (CF, CR, CR2, and CR3).
Detailed phylogenetic trees were generated using MEGAX (i.e., an integrated tool for automatic and manual sequence alignment). The alignment was initially done by using the program MUSCLE, and then it was generated with Maximum Likelihood parameters with 1,000 bootstraps.
In brief, Hawaiian SARS-CoV-2 strains that were deposited in the GenBank in March 2020 clustered with sequences from Wuhan, China, Sweden, and the state of New York (USA). The SARS-CoV-2 strains in this study clustered from the state of Washington (USA), as well as with sequences from China and Hawaii.
Furthermore, phylogenetic tree results suggest that the virus has been brought to Hawaii from many sources. Thirteen single nucleotide polymorphisms were decoded across 13 unique SARS-CoV-2 genomes within the S gene region – with one non-synonymous mutation (P681H) detected in the two Hawaii strains.
Importantly this notorious P681H mutation has distinctive and emerging characteristics, with an exponential increase in global frequency in comparison to the plateauing of the (currently universal) D614G mutation. Likewise, the P681H mutation is also a characteristic feature of the new SARS-CoV-2 variants found in the United Kingdom and Nigeria.
Significantly several mutations resulting in cysteine residues were also found, with potential consequences such as the disruption of the disulfide bridges in and around the receptor-binding domain of the viral spike glycoprotein.
The research actually demonstrates a partial sequence from the first SARS-CoV-2 strain that harbors the non-synonymous P681H mutation. Further studies are, therefore, warranted to analyze the pathogenicity and virulence of this mutation in the Hawaii strains and whether it can be considered a viral evasion mechanism to put off antibody recognition.
Corresponding author Dr Vivek R. Nerurkar, Ph.D. from the Department of Tropical Medicine, Medical Microbiology and Pharmacology John A. Burns School of Medicine told Thailand Medical News, "In Hawaii, Native Hawaiians and Pacific Islanders have a significantly high prevalence of SARS-CoV-2 when compared to other ethnic minorities and Whites. Characterizing viral sequences from these minority groups is important to better understand virus transmission and pathogenicity.”
Also, going forward, targeted sequence characterization will be necessary to determine the origin of multiple introductions of SARS-CoV-2 circulating in Hawaii, which can subsequently inform similar studies in other parts of the world.
In summary, COVID-19 in Hawaii and the pandemic originating in Wuhan in the 2019-2020 winter is still ongoing. The virus continues to mutate and the effects and outcomes of several of these mutations has yet to be elucidated. This study demonstrates a partial sequence from the first SARS-CoV-2 strain possessing the P681H non-synonymous mutation
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