RetroMAD1 for COVID-19

 RetroMAD1 has been reported as potentially beneficial for COVID-19 in the following studies.
COVID-19 involves the interplay of 350+ viral and host proteins and factors providing many therapeutic targets. Scientists have proposed 10,000+ potential treatments. c19early.org analyzes 210+ treatments. We have not reviewed RetroMAD1 in detail.
Chan et al., Anti-viral chimeric protein RetroMAD1™ potently block SARS-CoV-2 viral entry and propagation, Research Square, doi:10.21203/rs.3.rs-2712307/v1
Abstract COVID-19 is a disease caused by the highly transmissible and pathogenic SARS-CoV-2 virus. Since its first case was documented in 2019, it has rapidly widespread and has caused millions of deaths worldwide. Many intervention strategies targeting these proteins have been developed. However, frequently mutation of SARS-CoV-2 poses a challenge to the effectiveness of current treatments. Therefore, it is critical to develop new therapeutic drugs against this disease. In this present study, in silico approach was used to study the interaction between RetroMAD1™and SARS-CoV-2 proteins including Spike proteins (S), 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro). The interaction of these viral proteins and RetroMAD1™ was performed through HDOCK server and visualised using PyMOL. Docking results revealed that all the complexes of SARS-CoV-2 proteins binding with RetroMAD1™ have relatively high docking scores. The binding energy of RetroMAD1™ complexes with SARS-CoV-2 S, 3CLpro, PLpro were − 15, -12.3 and − 15.4, respectively. RetroMAD1™antiviral efficiency and cytotoxicity was also evaluated using EpiAirway™ Model. In vitro validation of viral inhibitory effect of RetroMAD1™was performed with 3CLpro Inhibition Assay. The outcome showed that RetroMAD1™ represents a potential drug candidate against SARS-CoV-2 for its promising viral inhibitory effect.
Chan et al., Inhibition of SARS-CoV-2 3CL protease by the anti-viral chimeric protein RetroMAD1, Scientific Reports, doi:10.1038/s41598-023-47511-z
AbstractCOVID-19 results from SARS-CoV-2, which mutates frequently, challenging current treatments. Therefore, it is critical to develop new therapeutic drugs against this disease. This study explores the interaction between SARS-CoV-2 3CLpro and RetroMAD1, a well-characterized coronavirus protein and potential drug target, using in-silico methods. The analysis through the HDOCK server showed stable complex formation with a binding energy of -12.3, the lowest among reference drugs. The RetroMAD1-3CLpro complex underwent a 100 ns molecular dynamics simulation (MDS) in an explicit solvation system, generating various trajectories, including RMSD, RMSF, hydrogen bonding, radius of gyration, and ligand binding energy. MDS results confirmed intact interactions within the RetroMAD1-3CLpro complex during simulations. In vitro experiments validated RetroMAD1's ability to inhibit 3CLpro enzyme activity and prevent SARS-CoV-2 infection in human bronchial cells. RetroMAD1 exhibited antiviral efficacy comparable to Remdesivir without cytotoxicity at effective concentrations. These results suggest RetroMAD1 as a potential drug candidate against SARS-CoV-2, warranting further in vivo and clinical studies to assess its efficiency.