COVID-19 and malaria share similar pathogenic pathways with the angiotensin converting enzyme 2 as a central initiator of signals to stimulate host cellular responses which in some instances result in multi-organ affectation. These signaling proteins are either upregulated or downregulated with the consequences of provoking immune responses with varying tissue damages. The similarities in clinical presentations, associated complications and therapeutic responses to the repurposed medications (anti-malarial drugs being used as anti-viral molecules) for the treatment of the novel disease COVID-19 have stimulated enormous interest in the recent past. The major objectives in this regard are to define the association between these two disease entities and possibly unveil options for interventions. This paper therefore aims at reviewing the molecular interactions which these diseases possibly share in their pathogenesis and phenotypic expressions and make projections for future interventions.