The retrocyclin analogue RC-101 inhibits Ebola virus infection in vitro.

Background: Ebola virus (EBOV) is one of the deadliest infectious agents for humans and non-human primates and it is the etiological agent of Ebola Virus Disease (EVD). The ongoing outbreak of the EVD in the Democratic Republic of the Congo points to the urgent need for new antivirals as there are currently no approved treatments or prophylactics to prevent infection. The cyclic antimicrobial peptide retrocyclin RC-101 has been shown previously to have antiviral activity against several viruses, such as HIV-1, HSV1 and -2, influenza virus. RC-101 acts as a lectin that interacts with the carbohydrate moieties of glycoproteins affecting the ability of viruses to enter into target cells. Furthermore, it has been shown that RC-101 decreased both the lethality and clinical severity associated with influenza virus infection in mice, potentially acting through both TLR-dependent and TLR-independent mechanisms. Here, we evaluated the activity of RC-101 against EBOV, which owes some of its pathogenicity to excessive inflammation. Methods: A recombinant system based on the Vesicular Stomatitis virus expressing the luciferase reporter gene (rVSV-Luc) was adopted to evaluate the effect of RC-101 on EBOV infection of A549 cells. The rVSVLuc was pseudotyped with the Makona variant of the EBOV glycoprotein (GP) that provides to rVSVLuc the same tropism and entry pathway of EBOV. Results: We found that the pre-incubation of the GP-pseudotyped rVSV-Luc with RC-101 inhibited viral infection in a dose depended manner. Luciferase activity was reduced of more the 90 % by 2 hours of virus preincubation with 50 μg/mL of RC-101 before the addition of the virus to target cells. The same magnitude of virucidal effect was maintained upon an incubation of at least sixty minutes. Time of addition experiments will further dissect the RC-101 anti-EBOV mechanism of action. Conclusions: These findings suggest that RC-101 exploits a virucidal effect against the Ebola virus infection. The ability of RC-101 to affect the host innate-immunity response could make RC-101 a good candidate for the development of protocols for the prevention/treatment of EVD