Researchers identify defensins as potential anti-SARS-CoV-2 agents


A recent study conducted by Ohio State University, USA, and Fudan University, China, revealed that alpha-defensin human neutrophil peptide 1 (HNP1), a cationic antimicrobial peptide, can prevent severe respiratory distress. syndrome coronavirus 2 (SARS-CoV -2) from infecting cells by inhibiting the virus protein on the spike and disruption of spike -mediated viral envel – host cell membrane fusion. The study now applies to bioRxiv* preprint server.

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Induction of adaptive immunity by vaccination is a valuable strategy to combat the current intrusion of COVID-19. Although the current release of COVID-19 vaccines has shown good efficacy against SARS-CoV-2 infection and symptomatic disease, there remains a risk from newly released different viruses that may ‘g bypass vaccine -induced resistance by removing mutations that have emerged.

Due to the fact that a large proportion of individuals infected with SARS-CoV-2 remain asymptomatic, it is expected that at least in some cases, the virus can be eliminated by the natural immune system. Human alpha and beta-defensins are committed members of the innate immune system that show strong antimicrobial efficacy against a variety of pathogens, including human immunodeficiency virus (HIV), herpes simplex virus, influenza virus, and SARS- CoV.

In the present study, the scientists examined the effectiveness of an alpha defensin, human neutrophil peptide 1 (HNP1), and a retrocyclin, RC-101, against SARS-CoV-2 infection.

Causal observation

To evaluate the antiviral efficacy of HNP1 and RC-101, the scientists obtained two human cell lines that strongly express viral spike protein or human angiotensin-converting enzyme 2 (ACE2). By administering HNP1 or RC-101 in coconut, they observed that in the absence of serum, both HNP1 and RC-101 were able to completely inhibit the spike-ACE2 interaction. However, in the presence of serum, defensin -mediated inhibition was removed.

Use a spike-encoding pseudovirus-cell infection model, they found that preincubation of cells containing HNP1 or RC-101 did not influence the susceptibility to virus infection. However, preincubation of HNP1 or RC-101 with pseudovirus prior to infection caused infection to be prevented. These findings show that instead of influencing the host cell molecule ACE2, defensins directly modulate viral particles to prevent infection.

While studying the mechanism of action of defensins, they observed that HNP1 directly binds to recombinant spike protein at sub-micromolar concentrations. Because serum inhibited defensin activity, they examined whether HNP1 binds to the most serum protein album. The findings revealed that HNP1 has a 20-fold lower affinity for serum albumin, pointing to its high selectivity for viral spike protein.

With further investigation using differential scanning fluorimetry, they observed that both HNP1 and RC-101 could not damage the spike protein at micromolar concentrations.

To determine whether HNP1 and RC-101 can prevent infection by the true SARS-CoV-2 virus, they either precipitated the HNP1 virus or administered HNP1 to cell culture medium after the virus was added. Under the same condition, HNP1 strongly inhibits viral infection. Similar to previous experiments, serum inhibited the antiviral efficacy of HNP1 in a dose -dependent manner. However, when used in sufficiently high concentrations, HNP1 is able to prevent SARS-CoV-2 infection even in the presence of 10% serum.

HNP1 and RC101 inhibit SARS-CoV-2 spike-pseudotyped viral infection

Meaning of study

The study findings revealed that at sub-micromolar concentrations, defenses including HNP1 and RC-101 have the ability to neutralize SARS-CoV-2. Among defensins, retrocyclins are particularly promising because of their high strength, low toxicity, intolerance, and resistance to proteolytic degradation. In this context, there is evidence to suggest that retrocyclins may be used as topical antimicrobial agents to prevent sexually transmitted HIV infection.

Even if the findings show that defensins are less active in serum, scientists believe that HNP1 and RC-101 should be considered potential anti-COVID-19 agents for topical use.

*Important Notice

bioRxiv publishes preliminary scientific reports that have not been reviewed by colleagues and, therefore, are not considered conclusions, guiding clinical practice / health -related behavior, or treated as established information.



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