Predictive etiology of Long COVID oncogenesis through SARS-CoV-2 proteins and AKT1 molecular docking interactions

Abstract

Abstract Background: In 2019, the world witnessed an outbreak of SARS-CoV-2, whose retention for two months or more leads to long COVID. Several long-term staying viruses cause oncogenesis. We intended to find any such potential with SARS-CoV-2. A rigorous systematic analysis of viral oncogenic pathways and long COVID was conducted. SARS-CoV-2 affects glutamatergic and Protein Tyrosine Kinases 1 signalling, leading to molecular interference. AKT1 protein was analyzed for predictive interaction studies with structural and non-structural viral proteins. Molecular docking simulations were also carried out. Methods:Oncogenes were detected in SARS-CoV-2 protein sequence, using TAG database. AKT1 was selected as a high potential oncogenic factor and was modelled using SWISS-MODEL. Viral proteins structures were either downloaded from Protein Data Bank, otherwise modelled. Docking was performed using HDOCK server. Prediction of possible potential active sites was done using Protein Allosteric and Regulatory Site (PARS). Results: AKT1 showed very strong interactive potential with all viral proteins with docking scores less than -200, envelope protein being the most potently reactive. PARS analysis showed that there might be more than one potential active site. All proteins cavities satisfied the requirement for flexibility p-value. NSP5 showed great structural conservation. Conclusion: When SARS-CoV-2 stays in the body of infected person for extended time durations, it has a strong oncogenic potential. Given the host of cellular targets because of angiotensin-converting enzyme type-2 presence, any infected organ harboring the virus for longer terms might be at risk of developing cancer. We propose further molecular and case study investigations to assess this threat to full extent.