Ramping Up Antimicrobial Peptides Against Severe Acute Respiratory Syndrome Coronavirus-2

Abstract

Human-derived antimicrobial peptides (AMPs), such as defensins and cathelicidin LL-37, are members of the innate immune system and play a crucial role in early pulmonary defense against viruses. These AMPs achieve viral inhibition through a variety of mechanisms including, but not limited to, direct binding to virions, binding to and modulating host cell-surface receptors, blocking viral replication, and aggregation of viral particles and indirectly by functioning as chemokines to enhance or curb adaptive immune responses. Given the fact that we are in a pandemic of unprecedented severity and the urgent need for therapeutic options to combat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), naturally expressed AMPs and their derivatives have the potential to combat coronavirus disease 2019 (COVID-19) and impede viral infectivity in various ways. Provided the fact that development of effective treatments is an urgent public health priority, AMPs and their derivatives are being explored as potential prophylactic and therapeutic candidates. Additionally, cell-based platforms such as human mesenchymal stem cell (hMSC) therapy are showing success in saving the lives of severely ill patients infected with SARS-CoV-2. This could be partially due to AMPs released from hMSCs that also act as immunological rheostats to modulate the host inflammatory response. This review highlights the utilization of AMPs in strategies that could be implemented as novel therapeutics, either alone or in combination with other platforms, to treat CoV-2–infected individuals.

HBD-2 binds SARS-CoV-2 RBD and blocks viral entry: Strategy to combat COVID-19

“…Recent biophysical studies using bilayer interferometry predicted a strong binding interaction between LL-37, another human AMP, and the RBD (Wang et al, 2021a). This finding supports the idea that more than one AMP could be utilized, possibly in a ''cocktail'' to act as a potent blocking agent (Ghosh and Weinberg, 2021). Recent findings also highlight that neuropilin-1 (NRP1), is being utilized by CoV-2 to facilitate entry and infection (Cantuti-Castelvetri et al, 2020;Daly et al, 2020;Li and Buck, 2021)and time will tell if also blocking entry via NRP1 will be required to reduce CoV-2 infection.…”

Normal T and B Cell Responses Against SARS-CoV-2 in a Family With a Non-Functional Vitamin D Receptor: A Case Report

“…More studies of the general population are needed to fully understand the role of vitamin D in the immune response against SARS-CoV-2. Thus, vitamin D could play a role in dampening the cytokine storm seen in patients with severe COVID-19 and might also play a role in innate immunity against SARS-CoV-2 for example in generation of cathelicidin ( 10 , 40 , 41 ). We acknowledge, that the current findings in a family with a rare mutation can not necessarily be translated to the general population.…”

Emerging Roles of Vitamin D-Induced Antimicrobial Peptides in Antiviral Innate Immunity

“…Another mechanism through which LL-37 and other AMPs may intervene to block viral infections is through direct interaction with viral particles, destabilizing their envelopes [72]. Influenza A (InA) virus is a highly contagious pathogen responsible for annual global outbreaks [73].…”