FAKHRAVAC and BBIBP-CorV vaccine seeds’ binding to angiotensin-converting enzyme 2: A comparative molecular dynamics study

Abstract

AbstractBackgroundSafety and efficacy of the SARS-CoV-2 inactivated vaccines have been question since the emergence of SARS-CoV-2 variants of concern (VOCs). Using residue fluctuations and statistically comparing RMSF values, have escalated the understanding of the binding dynamics of the viral proteins to their receptors and here in this study, we compared the interaction between inactivated spike proteins (representing FAKHRAVAC and BBIBP-CorV vaccines seed) and the human Angiotensin-Converting Enzyme 2 (hACE2) receptor.MethodologyThrough 100 set of accelerated 1 ns comparative molecular dynamics simulations, we analyze the binding dynamics and energy components of these interactions and compared residue backbone fluctuations using entropy and statistics including KL-Divergence and KS-test.Principal FindingsOur results reveal that FAKHRAVAC and Sinopharm exhibit similar binding dynamics and affinity to hACE2. Further examination of residue-wise fluctuations highlights the common behavior of binding key residues and mutation sites between the two vaccines. However, subtle differences in residue fluctuations, especially at critical sites like Q24, Y435, L455, S477, Y505, and F486, raise the possibility of distinct efficacy profiles.ConclusionThese variations may influence vaccine immunogenicity and safety in response to evolving SARS-CoV-2 variants. The study underscores the importance of considering residue-wise fluctuations for understanding vaccine-pathogen interactions and their implications for vaccine design.Author summaryIt is fundamentally important to ensure the safety and efficacy of the FAKHRAVAC, as an inactivated vaccine candidate for SARS-CoV-2. Considering the previously published pre-clinical and clinical findings about the similarity of the FAKHRAVAC’s safety and efficacy in comparison to the BBIBP-CorV vaccine seed (which is recalled as Sinopharm), it is necessary to gain more insights into structure and function of this vaccine at the molecular level, as well. Since the binding dynamics of the viral proteins to their receptor can imply the vaccine’s immunogenicity and mechanism-of-action, binding dynamics of a vaccine candidate must be studied comprehensively. Hereby, we have compared binding dynamics of the FAKHRAVAC and Sinopharm vaccine seeds to the SARS-CoV-2 spike protein’s receptor, the ACE2. We took advantage of a comparative molecular dynamics simulation approach to effectively compare binding dynamics using atom fluctuations and at the residue level to ensure the resolution of this study. We have found similar binding dynamics and binding mechanics between these two vaccines, validating the pre-clinical and clinical findings computationally, as well as highlighting residues with different fluctuations and discussed their potential roles.