Putative antimicrobial peptide 1

Antimicrobial resistance is considered a health issue worldwide. This public health problem underscores the importance of searching for new antimicrobial molecules with different mechanisms of action. Leaf transcriptomes were used to search and develop synthetic antimicrobial peptides derived from mRNA sequences. The in silico search for new AMPs from the L. rotundifolia and L. alba transcriptomes allowed the identification of 120 putative peptide mRNA sequences. Eight of them fitted into optimal parameters and were translated and chemically synthesized antimicrobial peptides. Their biological activity was tested in both Gram-positive and Gram-negative bacteria against which they exhibited antibacterial activity. However, they showed an important hemolytic effect. Afterwards, two active peptides showing bactericidal activity isolated from each plant transcriptome tested were modified and modeled in 11 new variants to increase their antimicrobial activity and stability and to reduce or eliminate their hemolytic effect from their original peptides. The La-AMP1 (MSLLERKLLMHFLRV) the original peptide from L. alba showed a 52% hemolytic effect while the derived peptide La-AMP1a (GLMKLLRELLHMFSRVG) had its hemolytic effect reduced to 0.5% at 128 μg.mL-1. Similarly, we observed that the original peptide from L. rotundifolia, Lr-AMP1 (MRIGLRFVLM), displayed a 71.5% hemolytic effect, while its derived peptide Lr-AMP1f (GSVLRAIMRMFAKLMG) showed 0% hemolysis at 128 μg.mL-1, tested with fresh human erythrocytes. Our results indicate a promising method for the search for novel antimicrobial agents with reduced or zero hemolytic effect, as well as prediction and optimization of their activity from plant mRNA libraries.

The SARS-CoV-2 virus responsible for the COVID-19 pandemic has generated an explosion of interest both in the mechanisms of infection leading to dissemination and expression of this disease, and in potential risk factors that may have a mechanistic basis for disease propagation or control. Vitamin D has emerged as a factor that may be involved in these two areas. The focus of this article is to apply our current understanding of vitamin D as a facilitator of immunocompetence both with regard to innate and adaptive immunity and to consider how this may relate to COVID-19 disease. There are also intriguing potential links to vitamin D as a factor in the cytokine storm that portends some of the most serious consequences of SARS-CoV-2 infection, such as the acute respiratory distress syndrome. Moreover, cardiac and coagulopathic features of COVID-19 disease deserve attention as they may also be related to vitamin D. Finally, we review the current clinical data associating vitamin D with SARS-CoV-2 infection, a putative clinical link that at this time must still be considered hypothetical.

Vitamin D, best known for its role in skeletal health, has emerged as a key regulator of innate immune responses to microbial threat. In immune cells such as macrophages, expression of CYP27B1, the 25-hydroxyvitamin D 1α-hydroxylase, is induced by immune-specific inputs, leading to local production of hormonal 1,25-dihydroxyvitamin D (1,25D) at sites of infection, which in turn directly induces the expression of genes encoding antimicrobial peptides. Vitamin D signaling is active upstream and downstream of pattern recognition receptors, which promote front-line innate immune responses. Moreover, 1,25D stimulates autophagy, which has emerged as a mechanism critical for control of intracellular pathogens such as M. tuberculosis. Strong laboratory and epidemiological evidence links vitamin D deficiency to increased rates of conditions such as dental caries, as well as inflammatory bowel diseases arising from dysregulation of innate immune handling intestinal flora. 1,25D is also active in signaling cascades that promote antiviral innate immunity; 1,25D-induced expression of the antimicrobial peptide CAMP/LL37, originally characterized for its antibacterial properties, is a key component of antiviral responses. Poor vitamin D status is associated with greater susceptibility to viral infections, including those of the respiratory tract. Although the severity of the COVID-19 pandemic has been alleviated in some areas by the arrival of vaccines, it remains important to identify therapeutic interventions that reduce disease severity and mortality, and accelerate recovery. This review outlines of our current knowledge of the mechanisms of action of vitamin D signaling in the innate immune system. It also provides an assessment of the therapeutic potential of vitamin D supplementation in infectious diseases, including an up-to-date analysis of the putative benefits of vitamin D supplementation in the ongoing COVID-19 crisis.