<i>In silico</i>approach for designing of a multi-epitope based vaccine against novel Coronavirus (SARS-COV-2)

Saha, Ratnadeep; Burra, Prasad

doi:10.1101/2020.03.31.017459

Cited by 24 publications

(25 citation statements)

References 27 publications

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“…At the same time, significant progress towards the isolation and design of vaccines (mRNA-1273 vaccine © 2020 Moderna, Inc) and neutralizing antibodies 9 has been made. A computational study identified the structural basis for multi-epitope vaccines 10,11 whereas in another study, the glycosylation patterns of the spike SARS-CoV-2 protein were computationally deduced 12 . In one study 13 , fully human single domain anti-SARS-CoV-2 antibodies with sub-nanomolar affinities were identified from a phage-displayed single-domain antibody library by grafting naïve CDRs into framework regions of an identified human germline IGHV allele using SARS-CoV-2 RBD and S1 protein as antigens.…”

Section: Mainmentioning

confidence: 99%

De novo design of high-affinity antibody variable regions (Fv) against the SARS-CoV-2 spike protein

Boorla

Chowdhury

Maranas

2020

Preprint

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1The emergence of SARS-CoV-2 is responsible for the pandemic of respiratory disease known as COVID-1 2 19, which emerged in the city of Wuhan, Hubei province, China in late 2019. Both vaccines and targeted 1 3 therapeutics for treatment of this disease are currently lacking. Viral entry requires binding of the viral 1 4 spike receptor binding domain (RBD) with the human angiotensin converting enzyme (ACE2). In an 1 5 3 1 (Cellex, GeneTex etc.) for the development of antibody-based tests for SARS-CoV-2 detection are 3 2 ongoing 8 . At the same time, significant progress towards the isolation and design of vaccines (mRNA-3 3 1273 vaccine © 2020 Moderna, Inc) and neutralizing antibodies 9 has been made. A computational study : bioRxiv preprint identified the structural basis for multi-epitope vaccines 10,11 whereas in another study, the glycosylation 3 5 patterns of the spike SARS-CoV-2 protein were computationally deduced 12 . In one study 13 , fully human 3 6 single domain anti-SARS-CoV-2 antibodies with sub-nanomolar affinities were identified from a phage-3 7 displayed single-domain antibody library by grafting naïve CDRs into framework regions of an identified 3 8 human germline IGHV allele using SARS-CoV-2 RBD and S1 protein as antigens. In another study 14 , a 3 9 human antibody 47D11 was identified to have cross neutralizing effect on SARS-CoV-2 by screening 4 0 through a library of SARS-Cov-1 antibodies. In two other studies, potent neutralizing antibodies were 4 1 isolated from the sera of convalescent COVID-19 patients 15,16 . To the best of our knowledge, none of 4 2 these neutralizing antibody sequences are publicly available. In another very encouraging study 17 , human 4 3 antibody CR3022 (which is neutralizing against SARS-CoV-1 18 ) has been shown to bind to SARS-CoV-2 4 4 RBD in a cryptic epitope but without a neutralizing effect for SARS-CoV-2 in vitro. Moreover, we did 4 5 not find any studies that performed guided design of high affinity antibodies against specific epitopes of 4 6 SARS-CoV-2 proteins such as targeting the spike protein and subsequently prevent its binding with 4 7 human ACE2. 8 9Motivated by these shortcomings, here we explore the de novo design of antibody variable regions For each one of the 3,234 spike poses, OptMAVEn-2.0 identified a variable region combination 9 3 composed of end-to-end joined V*, CDR3, and J* region parts that minimized the Rosetta binding energy 9 4 between the variable region and spike epitope formed by the seven residues. As part of OptMAVEn-2.0, 9 5 the combinatorial optimization problem was posed and solved as a mixed-integer linear programming 9 6 (MILP) problem using the cplex solver 26 . The solution of this problem identifies, for each one of the spike 9 7 poses, the complete design of the variable region using parts denoted as HV*, HCDR3, HJ* for the heavy 9 8 chain H and L/KV*, L/KCDR3 and L/KJ* for the light chain-L/K. Only 173 antigen-presenting poses out 9 9 of 3,234 explored, yielded non-clashing antigen-antibody complexes. These 173 poses ...

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Section: Mainmentioning

confidence: 99%

De novo design of high-affinity antibody variable regions (Fv) against the SARS-CoV-2 spike protein

Boorla

Chowdhury

Maranas

2020

Preprint

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“…All the three CTL and two HTL MPVs were fitting into the ectodomain region of TLR3 receptor (Figure 7). T cell immune response driving long-term robust adaptive immunity in the vast majority of the population (Abdelmageed et al, 2020;Ahmed et al, 2020;Akhand et al, 2020;An et al, 2000;Banerjee et al, 2020;Baruah et al, 2020;Bhattacharya et al, 2020;Fast et al, 2020;Gragert et al, 2013;Gupta et al, 2020;Herst et al, 2020;Ismail et al, 2020;Khan et al, 2020;Lee et al, 2020;Liu et al, 2020;Lu et al, 2014;Mitra et al, 2020;Nerli et al, 2020;Poran et al, 2020;Ramaiah et al, 2020;Saha et al, 2020;Sheikhshahrokh et al, 2020;Singh et al, 2020;Srivastava et al, 2020a;Srivastava et al, 2020b;ul Qamar et al, 2020;Vashi et al, 2020;Yazdani et al, 2020). Numerous highly antigenic regions have also been reported from SARS-CoV-2 proteins which have been recognized on the basis of large population coverage by favorable binding with large number of HLA allele distributed amongst different ethnic human population worldwide (Grifoni et al, 2020b;Yarmarkovich and Warrington et al, 2020).…”

Section: Screening Of Potential Epitopes From Sars-cov-2 Proteomementioning

confidence: 99%

Computationally validated SARS-CoV-2 CTL and HTL Multi-Patch Vaccines designed by reverse epitomics approach, shows potential to cover large ethnically distributed human population worldwide

Srivastava

Verma

Kamthania³

et al. 2020

Preprint

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Background: The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a positive-sense single-stranded RNA coronavirus responsible for the ongoing 2019-2020 COVID-19 outbreak. The highly contagious COVID-19 disease has spread to 216 countries in less than six months. Though several vaccine candidates are being claimed, an effective vaccine is yet to come. In present study we have designed and theoretically validated novel Multi-Patch Vaccines against SARS-CoV-2. Methodology: A novel reverse epitomics approach, overlapping-epitope-clusters-to-patches method is utilized to identify multiple antigenic regions from the SARS-CoV-2 proteome. These antigenic regions are here termed as Ag-Patch or Ag-Patches, for Antigenic Patch or Patches. The identification of Ag-Patches is based on clusters of overlapping epitopes rising from a particular region of SARS-CoV-2 protein. Further, we have utilized the identified Ag-Patches to design Multi-Patch Vaccines (MPVs), proposing a novel methodology for vaccine design and development. The designed MPVs were analyzed for immunologically crucial parameters, physiochemical properties and cDNA constructs. Results: We identified 73 CTL (Cytotoxic T-Lymphocyte), 49 HTL (Helper T-Lymphocyte) novel Ag-Patches from the proteome of SARS-CoV-2. The identified Ag-Patches utilized to design MPVs cover 768 (518 CTL and 250 HTL) overlapping epitopes targeting different HLA alleles. Such large number of epitope coverage is not possible for multi-epitope vaccines. The large number of epitopes covered implies large number of HLA alleles targeted, and hence large ethnically distributed human population coverage. The MPVs:Toll-Like Receptor ectodomain complex shows stable nature with numerous hydrogen bond formation and acceptable root mean square deviation and fluctuation. Further, the cDNA analysis favors high expression of the MPVs constructs in human cell line. Conclusion: Highly immunogenic novel Ag-Patches are identified from the entire proteome of SARS CoV-2 by a novel reverse epitomics approach. We conclude that the novel Multi-Patch Vaccines could be a highly potential novel approach to combat SARS-CoV-2, with greater effectiveness, high specificity and large human population coverage worldwide.

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“…Several recent articles have suggested that SARS-CoV-2 proteome fragments are important to the viral lifecycle, several of which are conserved in the Coronaviridae family and which are possible targets as epitopes [15][16][17][18][19][20][21][22] . This is of importance since the choice of attack points is crucial to the success of the therapy (drug design) or prevention (vaccine design).…”

Section: Introductionmentioning

confidence: 99%

Common low complexity regions for SARS-CoV-2 and human proteomes as potential multidirectional risk factor in vaccine development

Gruca

Ziemska-Legięcka

Jarnot

et al. 2020

Preprint

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The rapid spread of the COVID-19 demands immediate response from the scientific communities. Appropriate countermeasures mean thoughtful and educated choice of viral targets (epitopes). There are several articles that discuss such choices in the SARS-CoV-2 proteome, other focus on phylogenetic traits and history of the Coronaviridae genome/proteome. However none consider viral protein low complexity regions (LCRs). Recently we created the first methods that are able to compare such fragments. We show that five low complexity regions (LCRs) in three proteins (nsp3, S and N) encoded by the SARS-CoV-2 genome are highly similar to regions from human proteome. As many as 21 predicted T-cell epitopes and 27 predicted B-cell epitopes overlap with the five SARS-CoV-2 LCRs similar to human proteins. Interestingly, replication proteins encoded in the central part of viral RNA are devoid of LCRs. Similarity of SARS-CoV-2 LCRs to human proteins may have implications on the ability of the virus to counteract immune defenses. The vaccine targeted LCRs may potentially be ineffective or alternatively lead to autoimmune diseases development. These findings are crucial to the process of selection of new epitopes for drugs or vaccines which should omit such regions.

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In silicoapproach for designing of a multi-epitope based vaccine against novel Coronavirus (SARS-COV-2)

Cited by 24 publications

References 27 publications

De novo design of high-affinity antibody variable regions (Fv) against the SARS-CoV-2 spike protein

De novo design of high-affinity antibody variable regions (Fv) against the SARS-CoV-2 spike protein

Computationally validated SARS-CoV-2 CTL and HTL Multi-Patch Vaccines designed by reverse epitomics approach, shows potential to cover large ethnically distributed human population worldwide

Common low complexity regions for SARS-CoV-2 and human proteomes as potential multidirectional risk factor in vaccine development

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