A domain-based vaccine construct against SARS-CoV-2, the causative agent of COVID-19 pandemic: development of self-amplifying mRNA and peptide vaccines

Pourseif, Mohammad M.; Parvizpour, Sepideh; Jafari, Behzad; Dehghani, Jaber; Naghili, Behrooz; Omidi, Yadollah

doi:10.34172/bi.2021.11

Cited by 45 publications

(46 citation statements)

References 115 publications

(133 reference statements)

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“…Some of the collected SNP residue positions do not present in the existed PDB structures. To fix this issue, we have used the previous research studies as an example and implemented them in this study to construct the three-dimensional (3-D) conformation of the native S-protein [ [33] , [34] , [35] , [36] , [37] , [38] ]. Hence, we used the I-TASSER server [ 39 ] to model the native S-protein.…”

Section: Methodsmentioning

confidence: 99%

“…It is a threading-based structure prediction program which used to generate the three-dimensional structure of proteins from their amino acid sequence. Some recent studies opted for the threading approach to model the protein to check the interaction with other biological molecules [ [33] , [34] , [35] , [36] , [37] , [38] ]. I-TASSER produces great quality model predictions of three-dimensional structures from amino acid sequences.…”

Section: Methodsmentioning

confidence: 99%

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Investigation of nonsynonymous mutations in the spike protein of SARS-CoV-2 and its interaction with the ACE2 receptor by molecular docking and MM/GBSA approach

Aljindan

Al‐Subaie

Al-Ohali

et al. 2021

Computers in Biology and Medicine

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COVID-19 is an infectious and pathogenic viral disease caused by SARS-CoV-2 that leads to septic shock, coagulation dysfunction, and acute respiratory distress syndrome. The spreading rate of SARS-CoV-2 is higher than MERS-CoV and SARS-CoV. The receptor-binding domain (RBD) of the Spike-protein (S-protein) interacts with the human cells through the host angiotensin-converting enzyme 2 (ACE2) receptor. However, the molecular mechanism of pathological mutations of S-protein is still unclear. In this perspective, we investigated the impact of mutations in the S-protein and their interaction with the ACE2 receptor for SAR-CoV-2 viral infection. We examined the stability of pathological nonsynonymous mutations in the S-protein, and the binding behavior of the ACE2 receptor with the S-protein upon nonsynonymous mutations using the molecular docking and MM_GBSA approaches. Using the extensive bioinformatics pipeline, we screened the destabilizing (L8V, L8W, L18F, Y145H, M153T, F157S, G476S, L611F, A879S, C1247F, and C1254F) and stabilizing (H49Y, S50L, N501Y, D614G, A845V, and P1143L) nonsynonymous mutations in the S-protein. The docking and binding free energy (ddG) scores revealed that the stabilizing nonsynonymous mutations show increased interaction between the S-protein and the ACE2 receptor compared to native and destabilizing S-proteins and that they may have been responsible for the virulent high level. Further, the molecular dynamics simulation (MDS) approach reveals the structural transition of mutants (N501Y and D614G) S-protein. These insights might help researchers to understand the pathological mechanisms of the S-protein and provide clues regarding mutations in viral infection and disease propagation. Further, it helps researchers to develop an efficient treatment approach against this SARS-CoV-2 pandemic.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Investigation of nonsynonymous mutations in the spike protein of SARS-CoV-2 and its interaction with the ACE2 receptor by molecular docking and MM/GBSA approach

Aljindan

Al‐Subaie

Al-Ohali

et al. 2021

Computers in Biology and Medicine

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“…Deep mutational scanning of the effect that amino acid substitutions make on RBD expression and ACE2 binding has been performed in a yeast display system [ 11 ]. This study is targeted at informing regions that are likely to be more evolutionary restricted, for vaccine design [ 12 ], but it is also valuable for assessing the structural and functional importance of residues for which computational work provides predictions, and is relevant for small molecule drug screens [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

A model for pH coupling of the SARS-CoV-2 spike protein open/closed equilibrium

Warwicker

2021

Briefings in Bioinformatics

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative agent of the coronavirus disease 2019 (COVID-19) pandemic, is thought to release its RNA genome at either the cell surface or within endosomes, the balance being dependent on spike protein stability, and the complement of receptors, co-receptors and proteases. To investigate possible mediators of pH-dependence, pKa calculations have been made on a set of structures for spike protein ectodomain and fragments from SARS-CoV-2 and other coronaviruses. Dominating a heat map of the aggregated predictions, three histidine residues in S2 are consistently predicted as destabilizing in pre-fusion (all three) and post-fusion (two of the three) structures. Other predicted features include the more moderate energetics of surface salt–bridge interactions and sidechain–mainchain interactions. Two aspartic acid residues in partially buried salt-bridges (D290–R273 and R355–D398) have pKas that are calculated to be elevated and destabilizing in more open forms of the spike trimer. These aspartic acids are most stabilized in a tightly closed conformation that has been observed when linoleic acid is bound, and which also affects the interactions of D614. The D614G mutation is known to modulate the balance of closed to open trimer. It is suggested that D398 in particular contributes to a pH-dependence of the open/closed equilibrium, potentially coupled to the effects of linoleic acid binding and D614G mutation, and possibly also A570D mutation. These observations are discussed in the context of SARS-CoV-2 infection, mutagenesis studies, and other human coronaviruses.

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“…Currently, coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global problem [ 1 – 3 ]. This virus is known as the main cause of severe acute respiratory infections, pneumonia, kidney failure, or even death [ 4 ]. Despite, significant advances in the control of the wide variety of diseases such as cancers and infections [ 5 – 8 ], confronting the COVID-19 pandemic remains an outstanding challenge.…”

Section: Introductionmentioning

confidence: 99%

Micronutrient therapy and effective immune response: a promising approach for management of COVID-19

et al. 2021

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The escalating prevalence of coronavirus disease 2019 (COVID-19) worldwide, with an increased rate of morbidity and mortality, highlights an urgent need to develop more effective therapeutic interventions. Despite the authorized treatment against COVID-19 by the European Union (EU), the safety and effectiveness of this therapeutic strategy for a wide variety of patients have remained a significant challenge. In this respect, micronutrients such as vitamins and minerals, as essential factors, can be considered for improving the function of the immune system and accelerating the treatment procedure. Dietary supplements can attenuate vascular and inflammatory manifestations related to infectious diseases in large part due to their anti-inflammatory and antioxidant properties. Recently, it has been revealed that poor nutritional status may be one of the notable risk factors in severe COVID-19 infections. In the current review, we focus on the micronutrient therapy of COVID-19 patients and provide a comprehensive insight into the essential vitamins/minerals and their role in controlling the severity of the COVID-19 infection. We also discuss the recent advancements, challenges, negative and positive outcomes in relevance to this approach.

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A domain-based vaccine construct against SARS-CoV-2, the causative agent of COVID-19 pandemic: development of self-amplifying mRNA and peptide vaccines

Cited by 45 publications

References 115 publications

Investigation of nonsynonymous mutations in the spike protein of SARS-CoV-2 and its interaction with the ACE2 receptor by molecular docking and MM/GBSA approach

Investigation of nonsynonymous mutations in the spike protein of SARS-CoV-2 and its interaction with the ACE2 receptor by molecular docking and MM/GBSA approach

A model for pH coupling of the SARS-CoV-2 spike protein open/closed equilibrium

Micronutrient therapy and effective immune response: a promising approach for management of COVID-19

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