Emerging mutations in the SARS-CoV-2 variants and their role in antibody escape to small molecule-based therapeutic resistance

Chakraborty, Chiranjib; Bhattacharya, Manojit; Sharma, Ashish Ranjan

doi:10.1016/j.coph.2021.11.006

Cited by 36 publications

(39 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It blocks viral replication by acting as a nucleoside analogue inhibiting the RNA dependent RNA polymerase (RdRp) of Coronavirdae. Although no definitive study has been carried out on the Omicron variant, typical mutations in the RdRp associated with remdesivir resistance (e.g., V557L, V473F, N491S, F480L/S/C, P323L, or E802D) have not been described in this VOC yet [65]. However, new evidence on remdesivir intracellular signalling pathways is currently emerging as the possible implications on herpesviruses (HHV8 and EBV) reactivation [66].…”

Section: Antiviralsmentioning

confidence: 98%

Omicron Genetic and Clinical Peculiarities That May Overturn SARS-CoV-2 Pandemic: A Literature Review

Tiecco

Storti

Antoni

et al. 2022

IJMS

View full text Add to dashboard Cite

The Coronavirus disease 2019 (COVID-19) pandemic poses a great threat to global public health. The original wild-type strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has genetically evolved, and several variants of concern (VOC) have emerged. On 26 November 2021, a new variant named Omicron (B.1.1.529) was designated as the fifth VOC, revealing that SARS-CoV-2 has the potential to go beyond the available therapies. The high number of mutations harboured on the spike protein make Omicron highly transmissible, less responsive to several of the currently used drugs, as well as potentially able to escape immune protection elicited by both vaccines and previous infection. We reviewed the latest publication and the most recent available literature on the Omicron variant, enlightening both reasons for concern and high hopes for new therapeutic strategies.

show abstract

Section: Antiviralsmentioning

confidence: 98%

Omicron Genetic and Clinical Peculiarities That May Overturn SARS-CoV-2 Pandemic: A Literature Review

Tiecco

Storti

Antoni

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…However, several new SARS-CoV-2 variants have been generated with unique mutations in due course of time. The emerging variants of SARS-CoV-2 created a concern for antibody escape events ( 258 ). The preliminary study suggests that more mutations are localized in the antibody binding regions of S-glycoprotein.…”

Section: The Strategy and Insight In Vaccine Design Mabs Development ...mentioning

confidence: 99%

“…One such example is remdesivir, which targets RdRp to inhibit the virus replication. Several mutations are reported in the RdRp in the newly emerging variants ( 258 ). It creates a concern for the chemical components based on therapeutic escape or therapeutic resistance.…”

Section: The Strategy and Insight In Vaccine Design Mabs Development ...mentioning

confidence: 99%

A Detailed Overview of Immune Escape, Antibody Escape, Partial Vaccine Escape of SARS-CoV-2 and Their Emerging Variants With Escape Mutations

et al. 2022

Self Cite

View full text Add to dashboard Cite

The infective SARS-CoV-2 is more prone to immune escape. Presently, the significant variants of SARS-CoV-2 are emerging in due course of time with substantial mutations, having the immune escape property. Simultaneously, the vaccination drive against this virus is in progress worldwide. However, vaccine evasion has been noted by some of the newly emerging variants. Our review provides an overview of the emerging variants’ immune escape and vaccine escape ability. We have illustrated a broad view related to viral evolution, variants, and immune escape ability. Subsequently, different immune escape approaches of SARS-CoV-2 have been discussed. Different innate immune escape strategies adopted by the SARS-CoV-2 has been discussed like, IFN-I production dysregulation, cytokines related immune escape, immune escape associated with dendritic cell function and macrophages, natural killer cells and neutrophils related immune escape, PRRs associated immune evasion, and NLRP3 inflammasome associated immune evasion. Simultaneously we have discussed the significant mutations related to emerging variants and immune escape, such as mutations in the RBD region (N439K, L452R, E484K, N501Y, K444R) and other parts (D614G, P681R) of the S-glycoprotein. Mutations in other locations such as NSP1, NSP3, NSP6, ORF3, and ORF8 have also been discussed. Finally, we have illustrated the emerging variants’ partial vaccine (BioNTech/Pfizer mRNA/Oxford-AstraZeneca/BBIBP-CorV/ZF2001/Moderna mRNA/Johnson & Johnson vaccine) escape ability. This review will help gain in-depth knowledge related to immune escape, antibody escape, and partial vaccine escape ability of the virus and assist in controlling the current pandemic and prepare for the next.

show abstract

“…However, Omicron has been described as an immensely mutated variant containing an "unusual constellation of mutations" [22]. Therefore, understanding the mutation landscape of the Omicron variant is crucial, particularly the effect of mutations on antibody escape which has commonly been reported for SARS-CoV-2 variants [23]. A recent study revealed mutations in the RBD and NTD.…”

Section: Introductionmentioning

confidence: 99%

Omicron variant (B.1.1.529) of SARS-CoV-2: understanding mutations in the genome, S-glycoprotein, and antibody-binding regions

et al. 2022

Self Cite

View full text Add to dashboard Cite

The Omicron variant has been detected in nearly 150 countries. We analyzed the mutational landscape of Omicron throughout the genome, focusing the S-glycoprotein. We also evaluated mutations in the antibody-binding regions and observed some important mutations overlapping those of previous variants including N501Y, D614G, H655Y, N679K, and P681H. Various new receptor-binding domain mutations were detected, including Q493K, G496S, Q498R, S477N, G466S, N440K, and Y505H. New mutations were found in the NTD (Δ143-145, A67V, T95I, L212I, and Δ211) including one new mutation in fusion peptide (D796Y). There are several mutations in the antibody-binding region including K417N, E484A, Q493K, Q498R, N501Y, and Y505H and several near the antibody-binding region (S477N, T478K, G496S, G446S, and N440K). The impact of mutations in regions important for the affinity between spike proteins and neutralizing antibodies was evaluated. Furthermore, we examined the effect of significant antibody-binding mutations (K417N, T478K, E484A, and N501Y) on antibody affinity, stability to ACE2 interaction, and possibility of amino acid substitution. All the four mutations destabilize the antibody-binding affinity. This study reveals future directions for developing neutralizing antibodies against the Omicron variant. Supplementary Information The online version contains supplementary material available at 10.1007/s11357-022-00532-4.

show abstract

Emerging mutations in the SARS-CoV-2 variants and their role in antibody escape to small molecule-based therapeutic resistance

Cited by 36 publications

References 60 publications

Omicron Genetic and Clinical Peculiarities That May Overturn SARS-CoV-2 Pandemic: A Literature Review

Omicron Genetic and Clinical Peculiarities That May Overturn SARS-CoV-2 Pandemic: A Literature Review

A Detailed Overview of Immune Escape, Antibody Escape, Partial Vaccine Escape of SARS-CoV-2 and Their Emerging Variants With Escape Mutations

Omicron variant (B.1.1.529) of SARS-CoV-2: understanding mutations in the genome, S-glycoprotein, and antibody-binding regions

Contact Info

Product

Resources

About