Reinforcing our defense or weakening the enemy? A comparative overview of defensive and offensive strategies developed to confront COVID-19.

Developing effective strategies to confront coronavirus disease 2019 (COVID-19) has become one of the greatest concerns of the scientific community. In addition to the vast number of global mortalities due to COVID-19, since its outbreak, almost every aspect of human lives has changed one way or another. In the present review, various defensive and offensive strategies developed to confront COVID-19 are illustrated. The Administration of immune-boosting micronutrients/agents, as well as the inhibition of the activity of incompetent gatekeepers, including some host cell receptors (e.g. ACE2) and proteases (e.g. TMPRSS2), are some efficient defensive strategies. Antibody/phage therapies and specifically vaccines also play a prominent role in the enhancement of host defense against COVID-19. Nanotechnology, however, can considerably weaken the virulence of SARS-CoV-2, utilizing fake cellular locks (compounds mimicking cell receptors) to block the viral keys (spike proteins). Generally, two strategies are developed to interfere with the binding of spike proteins to the host cell receptors, either utilizing fake cellular locks to block the viral keys or utilizing fake viral keys to block the cellular locks. Due to their evolutionary conserved nature, viral enzymes, including 3CLpro, PLpro, RdRp, and helicase are highly potential targets for drug repurposing strategy. Thus, various steps of viral replication/transcription can effectively be blocked by their inhibition, leading to the elimination of SARS-CoV-2. Moreover, RNA decoy and CRISPR technologies likely offer the best offensive strategies after viral entry into the host cells, inhibiting the viral replication/assembly in the infected cells and substantially reducing the quantity of viral progeny.