Functional mutations of SARS-CoV-2: implications to viral transmission, pathogenicity and immune escape

Dang, Shengyuan; Ren, Lili; Wang, Jianwei

doi:10.1097/cm9.0000000000002158

Cited by 6 publications

(5 citation statements)

References 152 publications

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“…The study by Oulas et al demonstrates that the P13L mutation can influence both transmissibility and death rates. Specifically, this mutation is associated with a decrease in the number of deaths and cases per million 15 , 25 . For the P13L mutation, our experiments showed that it leads to structural stabilization.…”

Section: Discussionmentioning

confidence: 99%

“…Taking into account that viral proteins do not mutate singularly, and the impact on pathogenesis is likely influenced by the combination of multiple mutations in different proteins, it becomes a complicated task. Therefore, determining the relationship between mutations and disease outcomes requires a comprehensive analysis of various mutation combinations rather than focusing on individual mutations in isolation 12 , 15 .…”

Section: Introductionmentioning

confidence: 99%

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Impact of mutations on the stability of SARS-CoV-2 nucleocapsid protein structure

Muradyan,

Arakelov,

Sargsyan

et al. 2024

Sci Rep

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The nucleocapsid (N) protein of SARS-CoV-2 is known to participate in various host cellular processes, including interferon inhibition, RNA interference, apoptosis, and regulation of virus life cycles. Additionally, it has potential as a diagnostic antigen and/or immunogen. Our research focuses on examining structural changes caused by mutations in the N protein. We have modeled the complete tertiary structure of native and mutated forms of the N protein using Alphafold2. Notably, the N protein contains 3 disordered regions. The focus was on investigating the impact of mutations on the stability of the protein's dimeric structure based on binding free energy calculations (MM-PB/GB-SA) and RMSD fluctuations after MD simulations. The results demonstrated that 28 mutations out of 37 selected mutations analyzed, compared with wild-type N protein, resulted in a stable dimeric structure, while 9 mutations led to destabilization. Our results are important to understand the tertiary structure of the N protein dimer of SARS-CoV-2 and the effect of mutations on it, their behavior in the host cell, as well as for the research of other viruses belonging to the same genus additionally, to anticipate potential strategies for addressing this viral illness․

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of mutations on the stability of SARS-CoV-2 nucleocapsid protein structure

Muradyan,

Arakelov,

Sargsyan

et al. 2024

Sci Rep

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“…The impact of COVID-19 on individuals with diabetes appears to vary across different waves of the pandemic. This variation likely stems from changes in the virulence and pathogenicity of SARS-CoV-2 variants over time, as well as fluctuations in healthcare resources and accessibility [11].…”

Section: Discussionmentioning

confidence: 99%

"Covid-19 Outcomes in Individuals with Uncomplicated Diabetes Mellitus as their Sole Chronic Condition"

Argirova

2023

BJSTR

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Objective: This retrospective study aimed to examine the outcomes of cohorts of patients who had uncomplicated type II diabetes mellitus as their only documented chronic condition. We compared fully vaccinated and non-vaccinated populations within different sex and age groups, considering their clinical outcomes.Design: From March 2020 to June 2022, an extensive retrospective analysis was carried out using national patient data obtained from the database of the Ministry of Health of the Republic of Bulgaria, following a formal written request. The study encompassed a total of 1,126,946 confirmed COVID-19 patients.Results: Among the 1,126,946 confirmed COVID-19 patients included in this study, 0.33% (n=3,792) had type II diabetes mellitus as their sole chronic condition. Statistical analysis revealed significant findings in favor of the vaccinated cohorts, demonstrating reduced rates of hospitalizations [0.76 (95% CI 0.6550 to 0.9001); p=0.0011], ICU admissions [OR=0.38 (95% CI 0.2698 to 0.5282); p < 0.0001], in-hospital mortality [0.20 (95% CI 0.1126 to 0.3552); p<0.0001], and ICU-related mortality [0.25 (95% CI 0.0789 to 0.7860; p=0.0178]. Furthermore, the vaccinated cohort exhibited lower hospitalization rates specifically during the alpha wave of the pandemic. Statistically significant reductions in mortality rates were observed in the vaccinated cohorts during the beta [OR=0.01 (95% CI 0.0008 to 0.2085); p=0.0022], delta [OR=0.42 (95% CI 0.2636 to 0.6842); p=0.0004], and omicron [OR=0.20 (95% CI 0.1321 to 0.3132); p < 0.0001] waves. Additionally, within the vaccinated cohorts, those who received mRNA-based vaccines experienced higher and more significant reduction rates compared to those who received viral-vector-based vaccines. Conclusion:This retrospective analysis highlights a consistent pattern among patients with uncomplicated type II diabetes mellitus as the sole chronic condition who have received COVID-19 vaccination. Notably, vaccinated individuals have demonstrated a decrease in both the severity of COVID-19 cases and the rates of premature mortality.

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“…These mutations in the viral genome, have impacted various aspects of the pandemic response [1,2]. Notably, mutations in the spike gene and other accessory genes have been identified, affecting transmission dynamics, vaccine efficacy, disease severity, therapeutic interventions, diagnostic testing, and public health measures [3,4]. Within the spike gene, several mutations such as R203K, G204R, N501Y, E484K, L452R, and E484Q have been identified, which have the potential to increase viral replication, fitness, and immune evasion [3,4].…”

Section: Introductionmentioning

confidence: 99%

Emerging Mutations of SARS-COV-2 in Kenya

Mbogori,

Thiongo,

Deng

et al. 2024

Preprint

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Background: The rise of new SARS-CoV-2 mutations brought challenges and progress in the global fight against COVID-19. Mutations in spike and accessory genes affect transmission, vaccine efficacy, treatments, testing, and public health strategies. Monitoring emerging variants is crucial to halt virus spread. Methods: 44 nasopharyngeal/oropharyngeal swabs from Kenyan patients were sequenced with the Illumina platform. Galaxy's bioinformatic tools were used for genomic analysis. SARS-CoV-2 genome classification was done using PANGOLIN and mutation annotation with the COVID-19 Annotator tool. Results: The study showed 5 clades to be circulating in the region. 38(86%) were BA.1.1; 2(5%) were BA.1.1.1; 1(2%) was BA.1; 1(2%) was BA.1.14 and 2(5%) were AY.46. These clades had a cumulative of 173 mutations among them with 50 novel mutations. Forty-eight of these novel mutations occurred in a low frequency of 2.3% of the sequences tested while the other two, S:R214R, and NSP2:A555A, were for 43.2% and 18.2% of the cases respectively. Conclusions: The high-frequency novel mutations were synonymous mutations, a phenomenon that was previously viewed as phenotypically silent but recent studies indicate they can affect viral fitness with potential functional associations. These findings add to the understanding of the SARS-CoV-2 virus future evolutionary and immunological dynamics in the region

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Functional mutations of SARS-CoV-2: implications to viral transmission, pathogenicity and immune escape

Cited by 6 publications

References 152 publications

Impact of mutations on the stability of SARS-CoV-2 nucleocapsid protein structure

Impact of mutations on the stability of SARS-CoV-2 nucleocapsid protein structure

"Covid-19 Outcomes in Individuals with Uncomplicated Diabetes Mellitus as their Sole Chronic Condition"

Emerging Mutations of SARS-COV-2 in Kenya

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