Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a virus called``Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)."In the majority of patients, infection with COVID-19 may be asymptomatic or may cause only mild symptoms . However, in some patients, there can also be immunological problems, such as macrophage activation syndrome (CSS) that results in cytokine storm syndrome (CSS) and acute respiratory distress syndrome (ARDS). Comprehension of host-microbe communications is the critical aspect in the advancement of new therapeutics against infectious illnesses . Endogenous animal lectins, a class of proteins, may perceive non-self glycans found on microorganisms . Serum mannose-binding lectin (sMBL), as a part of the innate immune framework, recognizes a wide range of microbial microorganisms and activates complement cascade via an antibody-independent pathway . Although the molecular basis for the intensity of SARS-CoV-2 infection is not generally understood, scientific literature indicates that COVID-19 is correlated with unregulated activation of the complement in terms of disease severity . Disseminated intravascular coagulation (DIC), inflammation, and immune paralysis contribute to unregulated complement activation . Pre-existing genetic defects in MBL and their association with complement play a major role in immune response dysregulation caused by SARS-CoV-2 . In order to generate anti-complement-based therapies in Covid-19, an understanding of sMBL in immune response to SARS-CoV-2 and complement is therefore essential . This review highlights the role of endogenous sMBL and complement activation during SARS-CoV-2 infection and their therapeutic management by various agents, mainly plant lectins, since antiviral mannose-binding plant lectins (pMBLs) offer potential applications in the prevention and control of viral infections.