Status of mannose-binding lectin (MBL) and complement system in COVID-19 patients and therapeutic applications of antiviral plant MBLs

Abstract

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.

Man-Specific Lectins from Plants, Fungi, Algae and Cyanobacteria, as Potential Blockers for SARS-CoV, MERS-CoV and SARS-CoV-2 (COVID-19) Coronaviruses: Biomedical Perspectives

“…Owing to their smaller size, compared to other plant Man-specific lectins, Man-specific lectins from cyanobacteria such as CVN-N (cyanovirin), MVN (microvirin), and AH (actinohivin) from actinobacteria, have been deeply investigated for their anti-viral properties. In addition, only very few publications report the ability of Man-specific lectins from higher plants to interact with glycans of the coronavirus envelope [ 13 , 38 , 39 , 40 ].…”

MBL deficiency-causing B allele (rs1800450) as a risk factor for severe COVID-19

“…Our findings may have important implications such as the prioritization of individuals with B variants during vaccination strategies ( Gupta and Gupta, 2021 ) , or the encouragement of the affected individuals to receive mannose-specific plant lectins in an attempt to prevent a poor outcome after SARS-CoV-2 infection, as also suggested for other coronaviruses infections ( Medetalibeyoglu et al, 2021 ) .…”

“…In our study, we demonstrated that the presence of the B allele (rs1800450) of the MBL2 gene was significantly associated with a worse clinical phenotype in COVID-19 patients, and particularly with pneumonia development. The contribution of MBL deficiency in human infectious and non-infectious diseases has been established in several studies (reviewed by Gupta & Gupta, 2020) ( Gupta and Gupta, 2021 ). Thus, Liu et al reported that low levels of MBL are associated with an increased risk of community-acquired pneumonia and a greater risk of death ( Liu et al, 2014 ).…”

“…This seems a paradox, and we cannot exclude the possibility that our results may be affected by the small size and a possible diverse composition of our cohort . However, it should be emphasized that serum MBL levels are also affected by several factors including age, oxidative stress, smoking, second-hand smoke emission, exposure to fuel emissions, vitamin D levels and diet (with acidic diets reducing and alkaline diets increasing MBL levels) ( Chen et al, 2014 , Gupta and Gupta, 2021 , Sallenbach et al, 2011 , Tran et al, 2014 ). These factors could be the cause of no association between MBL deficiency and clinical presentation of the disease, as in our study most of the abovementioned data was not available.…”

Long noncoding RNAs in respiratory viruses: A review

“…Mannose‐binding lectin (MBL; also referred to as mannan‐binding lectin and mannose‐binding protein), is a pattern recognition innate immune molecule and involved in the protection of the host against viral infections. 89 , 90 IBV is a contagious avian coronavirus that can infect respiratory tract of chicken and in poultry industry is a major problem. 91 Zhang et al.…”