The unequivocal preponderance of biocomputation in clinical virology

Chun, Sechul; Muthu, Manikandan; Gopal, Judy; Paul, Diby; Kim, Doo Hwan; Enkhtaivan, Gansukh; Anthonydhason, Vimala

doi:10.1039/c8ra00888d

“…Computational virology is an emergent research field that takes advantage of the progress from molecular and structural biology, immunology, bioinformatics and related areas to foster the understanding of virus, their evolutionary dynamics in nature, infectivity, pathogenesis, cell/host-tropism, viral assembly and their molecular interactions in general (including how to predict epitopes, how to design specific neutralizing antibodies and basically any drug design & discovery related to viral infections) (Poveda-Cuevas et al, 2020;Ibrahim et al, 2018;Greber, 2019;Sharma et al, 2015;Sato et al, 2013;Backert and Kohlbacher, 2015;Chun et al, 2018;Viso et al, 2018). In particular, structural and interactive aspects can benefit from the solid foundations that computational molecular simulation methods such as Molecular Dynamics (MD) (Frenkel et al, 2001;Rapaport, 2004) and Monte Carlo (MC) (Frenkel et al, 2001;Binder, 1986) have achieved to probe the thermodynamic, dynamics and interactive properties of biomolecules in material science, food and pharma (see Refs.…”

Section: Theoretical Methodsmentioning

confidence: 99%

On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2

Giron

¹

,

Laaksonen

²

,

Silva

³

2020

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A new betacoronavirus named SARS-CoV-2 has emerged as a new threat to global health and economy. A promising target for both diagnosis and therapeutics treatments of the new disease named COVID-19 is the coronavirus (CoV) spike (S) glycoprotein. By constant-pH Monte Carlo simulations and the PROCEEDpKa method, we have mapped the electrostatic epitopes for four monoclonal antibodies and the angiotensin-converting enzyme 2 (ACE2) on both SARS-CoV-1 and the new SARS-CoV-2 S receptor binding domain (RBD) proteins. We also calculated free energy of interactions and shown that the S RBD proteins from both SARS viruses binds to ACE2 with similar affinities. However, the affinity between the S RBD protein from the new SARS-CoV-2 and ACE2 is higher than for any studied antibody previously found complexed with SARS-CoV-1. Based on physical chemical analysis and free energies estimates, we can shed some light on the involved molecular recognition processes, their clinical aspects, the implications for drug developments, and suggest structural modifications on the CR3022 antibody that would improve its binding affinities for SARS-CoV-2 and contribute to address the ongoing international health crisis.

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“…Computational virology is an emergent research field that takes advantage of the progress from molecular and structural biology, immunology, bioinformatics and related areas to foster the understanding of virus, their evolutionary dynamics in nature, infectivity, pathogenesis, cell/hosttropism, viral assembly and their molecular interactions in general (including how to predict epitopes, how to design specific neutralizing antibodies and basically any drug design & discovery related to viral infections). [27][28][29][30][31][32][33][34] In particular, structural and interactive aspects can benefit from the solid foundations that computational molecular simulation methods such as Molecular Dynamics (MD) 35,36 and Monte Carlo (MC) 35,37 have achieved to probe the thermodynamic, dynamics and interactive properties of biomolecules in material science, food and pharma (see refs. 38,39 for reviews).…”

Section: Theoretical Methodsmentioning

confidence: 99%

On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2

Giron

¹

,

Laaksonen

²

,

Silva

³

2020

Preprint

2

0

View full text Add to dashboard Cite

A new betacoronavirus named SARS-CoV-2 has emerged as a new threat to global health and economy. A promising target for both diagnosis and therapeutics treatments of the new disease named COVID-19 is the coronavirus (CoV) spike (S) glycoprotein. By constant-pH Monte Carlo simulations and the PROCEEDpKa method, we have mapped the electrostatic epitopes for four monoclonal antibodies and the angiotensin-converting enzyme 2 (ACE2) on both SARS-CoV-1 and the new SARS-CoV-2 S receptor binding domain (RBD) proteins. We also calculated free energy of interactions and shown that the S RBD proteins from both SARS viruses binds to ACE2 with similar affinities. However, the affinity between the S RBD protein from the new SARS-CoV-2 and ACE2 is higher than for any studied antibody previously found complexed with SARS-CoV-1. Based on physical chemical analysis and free energies estimates, we can shed some light on the involved molecular recognition processes, their clinical aspects, the implications for drug developments, and suggest structural modifications on the CR3022 antibody that would improve its binding affinities for SARS-CoV-2 and contribute to address the ongoing international health crisis.

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“…The major advantage of peptide-based vaccines is that their development is both safe and inexpensive in comparison to conventional techniques of vaccine production [8,9]. Interestingly, PVX-410, P10s-PADRE and TPIV200 are some of the chimeric peptide-based vaccines for TNBC that are currently in clinical phase trials.…”

Section: Introductionmentioning

confidence: 99%

Design of a potential Sema4A-based multi-epitope vaccine to combat triple-negative breast cancer: an immunoinformatic approach

Paranthaman

¹

,

Shanthi

²

2023

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Immunotherapy is revamping the therapeutic strategies for TNBC owing to its higher mutational burden and tumour-associated antigens. One of the most intriguing developments in cancer immunotherapy is the focus on peptide-based cancer vaccines. Thus, the current work aims to develop an efficient peptide-based vaccine against TNBC that targets Sema4A, which has recently been identified as a major regulator of TNBC progression. Initially, the antigenic peptides derived from Sema4A were determined and evaluated based on their capability to provoke immunological responses. The assessed epitopes were then linked with a suitable adjuvant (RpfB and RpfE) and appropriate linkers (AAY, GPGPG, KK and EAAAK) to preclude junctional immunogenicity. Eventually, docking and dynamics simulations are performed against TLR-2, TLR-4, TLR-7 and TLR-9 to assess the interaction between the vaccine construct and TLR receptors, as the TLR signalling pathway is critical in the host immune response. The developed vaccine was then exposed to in silico cloning and immune simulation analysis. The findings suggest that the designed vaccine could potentially evoke significant humoral and cellular immune responses in the intended organism. Considering these outcomes, the final multi-epitope vaccine could be employed to serve as an effective choice for TNBC management and may open new avenues for further studies.

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The unequivocal preponderance of biocomputation in clinical virology

Abstract: Biocomputation in clinical virology.

Cited by 6 publications

References 103 publications

On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2

On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2

On the interactions of the receptor-binding domain of SARS-CoV-1 and SARS-CoV-2 spike proteins with monoclonal antibodies and the receptor ACE2

Design of a potential Sema4A-based multi-epitope vaccine to combat triple-negative breast cancer: an immunoinformatic approach

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