Cell-surface receptors are the inviters of many potent pathogens that can adjust to any kind of circumstance for their existence. Many of these organisms are highly resistant to the currently existing drugs and mutate to new strains with high levels of pathogenesis, posing life-threatening consequences. Owing to such concerns, antiviral strategies are being assessed based on host cell receptor targeting. Many natural compounds with a tendency to strip off the cell surface receptors are under evaluation. Compounds that are non-toxic, patient friendly, and yield a quick output are essential for the current scenario. Drugs targeting the cell surface receptors should, therefore, be developed and standardized for the effective management of SARS-CoV-2 viral infection.