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1.
Virusdisease ; : 1-10, 2023 May 31.
Article in English | MEDLINE | ID: covidwho-20235879

ABSTRACT

D614G mutation plays a significant role in the transmissibility of SARS-CoV-2. Identification of other mutations related to D614G mutation within the Spike protein is pivotal as they might contribute to the pathogenicity of SARS-CoV-2. This study aims to analyze the mutation rate of furin cleavage site (FCS) region of Indonesian origin SARS-CoV-2 and to predict the effect of mutation against Spike priming efficiency by furin. A total of 375 sequences of Indonesian isolates obtained during the early pandemic were used for mutation analysis. Mutation analysis includes mutation pattern, variability, frequency of mutation, amino acid conservation, and mutation rate. The effect of mutation against Spike priming efficiency by furin protease from eight sequences with mutation in the FCS region was analyzed by protein-protein docking. We showed that mutations related to the G614 variant were increasing through time, in contrast to the D614 variant. The FCS region at the position 675-692 contained the most variable (66.67%) as well as the highest mutation frequency (85.92%) and has been observed to be the hotspot mutations linked to the D614G mutation. The D614G hotspot-FCS region (residue 600-700) had the highest amino acid change per site (20.8%) as well as the highest mutation rate as 1.34 × 10-2 substitution per site per year (95% CI 1.79 × 10-3-2.74 × 10-2), compared with other Spike protein regions. Mutations in the FCS region were the most common mutation found after the D614G mutation. These mutations were predicted to increase the Spike priming efficiency by furin. Thus, this study elucidates the importance of D614G mutation to other mutations located in the FCS region and their significance to Spike priming efficiency by furin. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-023-00827-w.

2.
Virus Genes ; 2023 Jun 13.
Article in English | MEDLINE | ID: covidwho-20235198

ABSTRACT

SARS-CoV-2 mutation is minimized through a proofreading function encoded by NSP-14. Most estimates of the SARS-CoV-2 mutation rate are derived from population based sequence data. Our understanding of SARS-CoV-2 evolution might be enhanced through analysis of intra-host viral mutation rates in specific populations. Viral genome analysis was performed between paired samples and mutations quantified at allele frequencies (AF) ≥ 0.25, ≥ 0.5 and ≥ 0.75. Mutation rate was determined employing F81 and JC69 evolution models and compared between isolates with (ΔNSP-14) and without (wtNSP-14) non-synonymous mutations in NSP-14 and by patient comorbidity. Forty paired samples with median interval of 13 days [IQR 8.5-20] were analyzed. The estimated mutation rate by F81 modeling was 93.6 (95%CI 90.8-96.4], 40.7 (95%CI 38.9-42.6) and 34.7 (95%CI 33.0-36.4) substitutions/genome/year at AF ≥ 0.25, ≥ 0.5, ≥ 0.75 respectively. Mutation rate in ΔNSP-14 were significantly elevated at AF ≥ 0.25 vs wtNSP-14. Patients with immune comorbidities had higher mutation rate at all allele frequencies. Intra-host SARS-CoV-2 mutation rates are substantially higher than those reported through population analysis. Virus strains with altered NSP-14 have accelerated mutation rate at low AF. Immunosuppressed patients have elevated mutation rate at all AF. Understanding intra-host virus evolution will aid in current and future pandemic modeling.

3.
Clinical Immunology: Principles and Practice, Sixth Edition ; : 525-541, 2022.
Article in English | Scopus | ID: covidwho-2323265

ABSTRACT

Human immunodeficiency virus (HIV)-1, the virus that causes HIV infection and acquired immunodeficiency syndrome (AIDS), has caused cases of infection recognized in the United States since the late 1970s. As scientists seek a cure for HIV, much has been learned about the interaction of the virus and the immune system. Recent advances in therapies used as tools for HIV treatment and prevention have resulted in a worldwide decrease in new infections, and public health campaigns are aimed at reducing new cases to a level signaling the end of the HIV epidemic. While organs and tissue systems may be damaged not only by HIV but also by the treatment of HIV with antiretroviral medications, people living with HIV can live a normal life span with appropriate medical management. The new epidemic affecting humankind, the novel coronavirus disease that emerged in 2019 (COVID-19) caused by the severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2), is disrupting HIV treatment and prevention programs worldwide and has laid bare health and healthcare disparities and inequalities existing in rich and poor countries alike. The effects of the COVID-19 pandemic on the HIV epidemic have yet to be realized. © 2023 Elsevier Ltd. All rights reserved.

4.
Cell Insight ; 1(3): 100029, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-2322401

ABSTRACT

The emergence of the SARS-CoV-2 Omicron variant poses a striking threat to human society. More than 30 mutations in the Spike protein of the Omicron variant severely compromised the protective immunity elicited by either vaccination or prior infection. The persistent viral evolutionary trajectory generates Omicron-associated lineages, such as BA.1 and BA.2. Moreover, the virus recombination upon Delta and Omicron co-infections has been reported lately, although the impact remains to be assessed. This minireview summarizes the characteristics, evolution and mutation control, and immune evasion mechanisms of SARS-CoV-2 variants, which will be helpful for the in-depth understanding of the SARS-CoV-2 variants and policy-making related to COVID-19 pandemic control.

5.
Methods in Molecular Biology ; 2621:v, 2023.
Article in English | EMBASE | ID: covidwho-2317522
6.
European Journal of Cancer ; 175(Supplement 1):S38, 2022.
Article in English | EMBASE | ID: covidwho-2300438

ABSTRACT

Background: Breast cancer accounts for 35-40% of cancer in women in Lebanese and Arab countries with 50% of patients (pts) diagnosed before age 50. Prevalence of pathogenic BRCA variants in high-risk pts is 5.6-20% (Abulkhair and El Saghir 2021). 7 BRCA1 and 7 BRCA2 pathogenic variants were found in 5.6% of 250 pts with high hereditary risk breast cancer using amplicon sequencing and MLPA (El Saghir 2015;Poulet 2016). We report results of Next Generation Sequencing (NGS) on selected cases based on Manchester Score. First report in ethnic Lebanese Arab pts. Method(s): Pts prospectively enrolled in 2009-2012. IRB approval secured. Pts signed informed consent. Data collected from medical records. Amplicon and MLPA was done on 250 patients. NGS was done on 100 cases with Manchester Score 14-56. DNAs of the 14 pts previously found to have a pathogenic variant (Manchester Score 10-59) were not re-sequenced. NGS on remaining 150 pts was not done due to Covid-19 pandemic and lack of additional funding. Result(s): NGS showed 7 pathogenic variants, 4 in PALB2 and 3 in ATM. No new BRCA variants were found. Two BRCA2 mutations noted by Amplicon/MLPA reported as VUS in 2015 are reclassified as pathogenic. Total BRCA2 pathogenic variants becomes 9. Total pathogenic variants 23. Risk of having hereditary breast cancer in pts with MS 10-59 is 20% (23/ 114), and at least 9.2% in the entire cohort (23/250). Age <=40 with family history (FH) carries 18.9% risk of harboring a pathogenic mutation while no FH, 1.4% (Table 1). All BRCA1 pts had triple negative and 7/9 BRCA2 pts had hormone receptor positive breast cancer. 4 unrelated pts shared the same c.1056_1057delGA PALB2 pathogenic variant thus we suggest this is a founder mutation in Lebanese Ethnic Arab population. Conclusion(s): Mutation rates in high hereditary risk pts with Manchester Score range 10-59 is 20%. Age <=40 with positive FH can be used to select pts for testing when resources are limited. Our data suggests that c.1056_1057delGA is a PALB2 founder mutation. No conflict of interest.Copyright © 2022 Elsevier Ltd. All rights reserved

7.
Clinical Immunology Communications ; 2:142-144, 2022.
Article in English | EMBASE | ID: covidwho-2299556

ABSTRACT

Influenza is an infectious respiratory disease caused by influenza A and B, which is a virus characterized by a high mutation rate with new strains appearing regularly, making regular booster vaccinations necessary. In this study, we evaluated the immune status of Influenza A and B by using ELISA. A questionnaire was utilized to appraise the immunization anamnesis and the stance on vaccination. In total, 202 probands participated in this study. 35.6% of the probands were vaccinated, 10.9% indicated a confirmed influenza infection. 88.1% had a positive influenza A titer, whereas a positive influenza B titer was determined in only 38.6%. Additionally, a correlation between vaccination and titer could be observed. In this study, we were able to show a higher vaccination rate in our cohort than the Austrian average. Additionally, a higher percentage showed a positive influenza A titer compared to influenza B titer.Copyright © 2022

8.
Mol Biol Evol ; 40(4)2023 04 04.
Article in English | MEDLINE | ID: covidwho-2292366

ABSTRACT

SARS-CoV-2 evolves rapidly in part because of its high mutation rate. Here, we examine whether this mutational process itself has changed during viral evolution. To do this, we quantify the relative rates of different types of single-nucleotide mutations at 4-fold degenerate sites in the viral genome across millions of human SARS-CoV-2 sequences. We find clear shifts in the relative rates of several types of mutations during SARS-CoV-2 evolution. The most striking trend is a roughly 2-fold decrease in the relative rate of G→T mutations in Omicron versus early clades, as was recently noted by Ruis et al. (2022. Mutational spectra distinguish SARS-CoV-2 replication niches. bioRxiv, doi:10.1101/2022.09.27.509649). There is also a decrease in the relative rate of C→T mutations in Delta, and other subtle changes in the mutation spectrum along the phylogeny. We speculate that these changes in the mutation spectrum could arise from viral mutations that affect genome replication, packaging, and antagonization of host innate-immune factors, although environmental factors could also play a role. Interestingly, the mutation spectrum of Omicron is more similar than that of earlier SARS-CoV-2 clades to the spectrum that shaped the long-term evolution of sarbecoviruses. Overall, our work shows that the mutation process is itself a dynamic variable during SARS-CoV-2 evolution and suggests that human SARS-CoV-2 may be trending toward a mutation spectrum more similar to that of other animal sarbecoviruses.


Subject(s)
COVID-19 , Severe acute respiratory syndrome-related coronavirus , Animals , Humans , SARS-CoV-2 , Mutation , Mutation Rate , Genome, Viral
9.
Coronaviruses ; 2(11) (no pagination), 2021.
Article in English | EMBASE | ID: covidwho-2275741

ABSTRACT

Background: RNA viruses evolve very fast, with a mutation rate of 103 to 105 base sub-stitution per nucleotides per copy. The mutation is a survival strategy for the viruses, which leads them to survive in the new host. Fitness is defined as the replication capacity of the virus in an ex-perimental setup. Generally, the large population passage of the virus leads to fitness gain, but the world data of the coronavirus infection and death shows the flattened curve with time. It is contra-dictory to the principle of fitness gain due to large population passage. The coronavirus is losing its potency but remains infectious as it is passaging into millions that leads to a decline in the death of COVID patients and high recovery rates. Fitness loss of coronaviruses attributed to a high level of mutation in the RNA genome as well as host immune response. The current outbreak of SARS CoV-2 is surfaced in December 2019 in Hubei province of China and considered as bats/pangolin origin, spreading 235 countries of the world, infecting nearly 31,664,104 people, and claimed nearly 972,221 lives as of September 24, 2020 (Death rate approximately 3%). This coronavirus has passaged into 31,664,104 people from the beginning of this pandemic until September 24, 2020. Now the virus is losing potency rather than being monotonous and continuous in producing virus-related complications. The population is still getting infected at the same rate, but the severity of the disease is reduced due to the potency of the virus diminished due to the passage effect as well as fitness loss of the virus due to high mutation rates. The death rate is reduced to 3% as compared to 6% in June 2020, when this paper was first submitted. Objective(s): The purpose of the study is to prove the fact that the coronavirus loses its potency with time but, they remain infective. It becomes more infectious due to mutation of the gene but loses the capacity to kill the host. Method(s): Since the WHO announces the COVID-19 outbreak is an emergency of international con-cern, every country in the world is taking many measures to mitigate the viral load to their popula-tion. Simultaneously, the WHO, CDC USA, CDC Europe, and much other organization is updating the COVID cases and death online daily as reported by the respective country. With the help of the COVID-19 outbreak data published by the European CDC and ourworldindata.org, we correlate the total cases of coronavirus and total death in the top ten affected countries in the world. We also link the trends of total cases vs. total death and total new cases vs. total new death related to COVID-19 in Germany, Spain, the United Kingdom, Italy, and New Zealand from January 30, 2020, until September 24, 2020. The reason to select these countries for the study is that these countries updating the COVID cases and deaths regularly and said to achieve the peak of COVID related infections and recovering from the pandemic. Result(s): We have tried to correlate the high mutation rate of the virus that leads to losing its potency to severe infection and death in the human. Viral extinction through high mutation could be considered as the new anti-viral strategies. Conclusion(s): Coronavirus is losing its potency to causing death to the human. The new infection is still being reported from every corner of the world, but the death rate is significantly decreasing.Copyright © 2021 Bentham Science Publishers.

10.
Nanotechnology Reviews ; 12(1), 2023.
Article in English | Scopus | ID: covidwho-2273002

ABSTRACT

Over the past two centuries, most pandemics have been caused by zoonotic RNA viruses with high mutation, infection, and transmission rates. Due to the importance of understanding the viruses' role in establishing the latest outbreak pandemics, we briefly discuss their etiology, symptomatology, and epidemiology and then pay close attention to the latest chronic communicable disease, SARS-CoV-2. To date, there are no generally proven effective techniques in the diagnosis, treatment, and spread strategy of viral diseases, so there is a profound need to discover efficient technologies to address these issues. Nanotechnology can be a promising approach for designing more functional and potent therapeutics against coronavirus disease 2019 (COVID-19) and other viral diseases. Moreover, this review intends to summarize examples of nanostructures that play a role in preventing, diagnosing, and treating COVID-19 and be a comprehensive and helpful review by covering notable and vital applications of nanotechnology-based strategies for improving health and environmental sanitation. © 2023 the author(s), published by De Gruyter.

11.
Journal of Laboratory and Precision Medicine ; 7 (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2269216

ABSTRACT

Background: This article is aimed to provide an updated landscape of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomic mutations emerged since its first identification and sequencing. Method(s): We downloaded and analyzed all mutations within the SARS-CoV-2 RNA genome submitted up to February 8, 2022 to the website of the National Center for Biotechnology Information (NCBI), which contains all variants in Sequence Read Archive (SRA) records compared to the prototype SARS-CoV-2 reference sequence NC_045512.2. Result(s): Our search identified 26,005 different mutations. The largest number of mutations was located within the gene encoding for the Nsp3 protein (20.7%), followed by the gene encoding for the spike protein (14.6%). Overall, 17,948/26,005 (69.0%) of these mutations interested single nucleotide positions, thus spanning over ~62% of the entire SARS-CoV-2 genome. Of all mutations, 61.5% were non-synonymous, whilst 17.4% of those in the gene encoding for the spike protein involved the sequence of the receptor binding domain, 59.2% of which were non-synonymous. When the number of mutations was expressed as ratio to the gene size, the highest ratio was found in the sequence encoding for ORF7a (ratio, 2.25), followed by ORF7b (ratio, 1.85), ORF8 (ratio, 1.60) and ORF3a (ratio, 1.48). The gene encoding for RNA-dependent RNA polymerase accounted for only 0.1% of all mutations, with considerably low ratio with the gene size (i.e., ratio, 0.01). Conclusion(s): The results of our analysis demonstrate that SARS-CoV-2 has enormously mutated since its first sequence has been identified over 2 years ago.Copyright © 2022 AME Publishing Company. All rights reserved.

12.
Coronaviruses ; 2(10) (no pagination), 2021.
Article in English | EMBASE | ID: covidwho-2265801

ABSTRACT

Corona viruses belong to the genus Corona virus with its high mutation rate in the Coro-naviridae. In this review article, the focus is on current status of research against SARS-CoV-2, various mobile apps launched to diagnose COVID-19 infection and status of prospective therapies available against COVID-19 virus in this early stage of COVID-19 outbreak.Copyright © 2021 Bentham Science Publishers.

13.
Coronaviruses ; 1(1):90-97, 2020.
Article in English | EMBASE | ID: covidwho-2265738

ABSTRACT

Coronaviruses (CoV) are a large group of viruses that can cause health disorders ranging from the usual cold to most severe diseases like Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). These viruses are generally found among animals. In atypical circumstances, these viruses can propagate to humans from animals. The spikes protruding from the membrane of the virus look like the sun's corona, hence the name 'coronavirus' has been given. Coronaviruses (CoV) belong to the species of Corona with a high mutation rate than the Coronaviridae. The objective of this review article was to investigate good strategies of treatment and preliminary analysis concerning the disease, and prevention in the early stage of the COVID-19 outbreak.Copyright © 2020 Bentham Science Publishers.

14.
Clinical Pharmacology and Therapeutics ; 113(Supplement 1):S84-S85, 2023.
Article in English | EMBASE | ID: covidwho-2254466

ABSTRACT

BACKGROUND: Exposure-response (E-R) analysis supported molnupiravir phase 3 dose selection based on viral load (VL) and mechanism of action (MOA) markers from phase 2.1 This analysis evaluated how well these biomarkers predict the E-R for hospitalization or death in phase 3. METHOD(S): The following E-R models were developed and compared: (1) logistic regression of the primary outcome (hospitalization or death) from phase 3, (2) VL change from baseline (CFB) from phase 2 and 3, and (3) low frequency nucleotide substitutions (LNS), a measure of MOA, from phase 2. Individual estimates of exposure were derived from population PK modeling of sparse samples collected in all patients. All work was performed using R v3.0 or later. RESULT(S): All E-R relationships were best represented by an Emax model with AUC50 estimates of 19,900, 10,260, and 4,390 nM*hr for hospitalization, day 5 VL CFB, and LNS mutation rate, respectively. Normalized E-R relationships were overlaid, illustrating consistency in E-R shape (Figure). Plasma NHC AUC0-12 was identified as the PK driver. Patients at 800 mg achieved near maximal response. CONCLUSION(S): E-R results support the dose of 800 mg Q12H for treatment of COVID-19. E-R relationships for MOA and virology biomarkers were consistent with the clinical E-R. (Figure Presented).

15.
Coronaviruses ; 2(12) (no pagination), 2021.
Article in English | EMBASE | ID: covidwho-2254336

ABSTRACT

The current COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has affected the large population across the globe by serious respiratory illness and death. Since the medicine for this new disease is yet to discover, the treatment op-tions against pandemic COVID-19 are very limited and unsatisfactory. Further, the hospitals, wherethe COVID-19 patients are admitted for treatment, are the major source of the spread of this virus, as it survives on the surfaces of inanimate objects for days. Therefore, hospitals have become hotspots for SARS-CoV-2 infection. The non-availability of quality personal protective equipment (PPE) and exposure to severe COVID patients have been major factors for the infection in millions of healthcare workers. However, developing an effective medicine has remained challenging due to its unpredictable mutation rate. Here, this article describes functionalized photocatalytic nanocoat-ings to destroy the COVID-19 virus, which can be applied on the surface of inanimate objects, such as paper, cloth, glass, wood, ceramic, metallic, and polymeric surfaces. With the supporting experimental results, various possible ways of killing the virus and its relevant mechanism are dis-cussed. This article provides new insights for developing nano solutions to address this COVID-19 issue.Copyright © 2021 Bentham Science Publishers.

16.
Coronaviruses ; 2(8) (no pagination), 2021.
Article in English | EMBASE | ID: covidwho-2251617

ABSTRACT

The emerging new COVID 2019 pandemic, which started in 2019 in China (Wuhan) and is caused by SARS-CoV-2, raises critical concerns due to high morbidity and mortality. As many patients are infected and the numbers still increase, this may suggest that there are different variants of the virus and some of them are more pathogenic. Besides, the virus is suspected to have various evolutionary pathways since SARS-CoV-2 belongs to the RNA viruses' family, which is characterized by a high mutation rate. Additionally, it is crucial to understand the life cycle of the virus to be able to urge antiviral studies. Genotyping studies about viruses are also important in order to understand the transmission and evolution of the virus. The genome of SARS-CoV-2 has a furin-like cleavage site in its S protein that may affect its pathogenicity. It was found that insertions and deletions in S protein have an impact on the transmission and fusion of the virus. The single nucleotide polymorphisms (SNP) genotypes are used to track the relationship of virus isolates. Se-quence alignment revealed the presence of hundreds of inter-host mutations during person-to-per-son transmission. Furthermore, genetic recombination provided a second mechanism for virus evo-lution. In this review, we highlight the life cycle of the virus and methods of virus evolution caused by mutations or recombination of viral genomes.Copyright © 2021 Bentham Science Publishers.

17.
Coronaviruses ; 2(5) (no pagination), 2021.
Article in English | EMBASE | ID: covidwho-2250710

ABSTRACT

The ongoing pandemic of the novel coronavirus SARS-CoV-2 (COVID-19) has created a major challenge for the public health worldwide. The reported cases indicate that the outbreak is more widespread than initially assumed. Around 18 million people have been infected with 689,000 reported deaths (August 2020;the number is increasing daily);with a high mutation rate, this virus poses an even more serious threat worldwide. The actual source of COVID-19 is still un-clear;even if the initial reports link it to the Chinese seafood wet market in Wuhan, other animals such as birds, snakes, and many small mammals including bats are also linked with this novel coro-navirus. The structure of the COVID-19 shows distinctive proteins among which spike proteins have a pivotal role in host cell attachment and virus-cell membrane fusion in order to facilitate virus infection. Currently, no specific antiviral treatment or vaccine is available. Various drug can-didates, including SARS-CoV and MERS-CoV protease inhibitors, neuraminidase inhibitors, RNA synthesis inhibitors, ACE2 inhibitors and lungs supportive therapy, are under trials. Cell-based therapy also appeared with remarkable treatment possibilities. In this article, we endeavored to succinctly cover the current and available treatment options, including pharmaceuticals, cell-based therapy, and traditional medicine. We also focused on the extent of damages by this novel coron-avirus in India, Pakistan, and Bangladesh;the strategies adopted and the research activities initiat-ed so far by these densely populated countries (neighboring China) are explained in this review.Copyright © 2021 Bentham Science Publishers.

18.
Dermatology Reports Conference: 27th National Italian Melanoma Intergroup Congress, IMI ; 14(Supplement 1), 2021.
Article in English | EMBASE | ID: covidwho-2249726

ABSTRACT

The proceedings contain 25 papers. The topics discussed include: altitude effect on melanoma epidemiology in the Veneto region: a pilot study;novel predisposition genes double a decreasing CDKN2A mutation rate: five years of (tele)- counselling and gene panel testing for hereditary melanoma within the Italian melanoma intergroup;genetic profiling of atypical deep penetrating NEVI (DPN);ultra-high frequency ultrasound monitoring of melanomas arising in congenital melanocytic nevi: a case series;a segmentation algorithm for skin melanoma regression;impact of the COVID-19 pandemic on primitive melanoma diagnoses at the IDI-IRCCS of Rome;a novel-algorithm combining static and dynamic features to identify melanoma in digital dermoscopy monitoring;and non-sentinel lymph node detection meanwhile sentinel lymph node biopsy in not-complete lymph node dissection era: a new technique for better staging and treating melanoma patients.

19.
Uncovering The Science of Covid-19 ; : 29-61, 2022.
Article in English | Scopus | ID: covidwho-2285462

ABSTRACT

The never-ending race for survival between the virus and its host continues to be a major challenge for biologistsas well as healthcare professionals. Owing to their simple genome organization, capacity for replication, mutation and adaptation - viruses can evolve rapidly, thereby posing a constant threat to human and other animal hosts The animal-human species barrier constitutes a considerable hurdle for zoonotic viruses, and often shields humans from the risk of new outbreaks. However, modern lifestyles and advanced technology have diminished geographic barriers, exposing humans to outbreaks initiated in one part of the world, and amplifying the associated health risks and economic losses across the globe. The novel SARS-CoV-2 outbreak that originated from Wuhan, China at the end of 2019 highlights that humans are continuously living under the threat of emerging zoonotic viruses. The Coronavirus disease 2019 (COVID-19) pandemic continues unabated despite theavailability and deployment of multiple approved vaccines and supportive therapies. Moreover, SARS-CoV-2 variants have emerged which contain mutations that promote viral transmissibility and/or virulence. Furthermore, these new variants have raised concerns over the protective efficacy of current vaccines and the susceptibility of unvaccinated individuals. This chapter discusses the potential causes and factors that influence viral fitness and host selection leading to the emergence of easily transmissible and highly pathogenic SARS-CoV-2 variants. © 2023 by World Scientific Publishing Co. Pte. Ltd.

20.
Coronaviruses ; 2(10) (no pagination), 2021.
Article in English | EMBASE | ID: covidwho-2284963

ABSTRACT

Background: SARS-nCOV-2 is a variant of the known SARS coronavirus family. The mutations in viruses are very rapid and can play a crucial role in the evolution or devolution of the organism. This has a direct impact on "host jumping" and the pathogenicity of the virus. Objective(s): The study aims to understand the frequency of genomic variations that have occurred in the virus affecting the Indian sub-population. The impact of variations translating to proteins and its consequences affecting protein stability and interaction were studied. Method(s): Phylogenetic analysis of the 140 genomes from the India region was performed, followed by SNP and Indel analysis of both CDS and non-CDS regions. This effort was followed by a prediction of mutations occurring in 8 proteins of interest and the impact on protein stability and prospective drug interactions. Result(s): Genomes showed variability in origin, and major branches can be mapped to the 2002 outbreak of SARS. The mutation frequency in CDS regions showed that 241 C >T, 3037 C >T, 2836 C >T, and 6312 C >A occurred in 81.5% of genomes mapping to major genes. Corresponding mutations were mapped to protein sequences. The effect of mutations occurring in spike glycoprotein, RNA dependent RNA polymerase, nsp8, nucleocapsid and 3c protease was also depicted. Conclusion(s): Whilst the mutations in spike glycoprotein showcased an increase in protein stability, the residues undergoing mutations were also a part of drug binding pockets for hydroxychloro-quine. Mutations occurring in other proteins of interest led to a decrease in protein stability. The mutations were also a part of drug binding pockets for Favipiravir, Remdesivir and Dexametha-sone. The work allows analyzing larger datasets to understand mutation patterns globally.Copyright © 2021 Bentham Science Publishers.

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