Exploring the Potency of Antiviral Marine Alkaloids Against Japanese encephalitis and Ebola virus: A Computational-Based Assessment for Drug Repurposing Applications

Abstract

In the twenty-first century, there have been a number of outbreaks, beginning with dengue, swine flu, Nipah, Ebola, chikungunya, and Zika, which were continuously outbreaks in some specific regions. The mosquito-transmitted flavivirus Japanese encephalitis (JE) virus, similar to dengue fever and West Nile viruses, and the negative-single-stranded Ebola virus (EBOV) are the two most emerging and the WHO's most-prioritized diseases. Natural products have always served as an alternative to mainstream drugs in emergencies. Thus, due to their excellent antiviral activity, the present study focused on marine alkaloids and assessed their potency against the JE and EBOV viruses. Using various bioinformatics tools, we selected 60 different antiviral marine alkaloids for anti-JE activity against RNA-dependent RNA polymerase (PDB ID: 4HDG), NS3-helicase (PDB ID: 2Z83), and NS5-protease (PDB ID: 4K6M), as well as anti-EBOV efficacy targeting nucleoprotein (PDB ID: 4Z9P), viral protein 24 (PDB ID: 4M0Q), and viral protein 40 (PDB ID: 3TCQ). Based on previous antiviral records with combined molecular docking scores, physicochemical, toxicity, pharmacokinetic, and drug-ability profiles, the researchers concluded that manzamines A, F, and X with 6-deoxymanzamine X and 8-hydroxymanzamine may be the best among all 60 candidates for JE and EV infection control. In summary, marine alkaloids exhibit excellent antiviral potency and need to be explored as more bioactive marine candidates for mainstream drug discovery, where bioinformatics tools are a more cost-effective, resource-efficient, and time-saving platform than traditional drug discovery modules to locate most lead candidates to be used in mainstream medicine for emerging health conditions.