Antiviral Strategies against Arthritogenic Alphaviruses

Abstract

Alphaviruses are members of the Togaviridae family that are mainly transmitted by arthropods such as mosquitoes. In the last decades, several alphaviruses have re-emerged, causing outbreaks worldwide. One example is the re-emergence of chikungunya virus (CHIKV) in 2004, which caused massive epidemics in the Indian Ocean region after which the virus dramatically spread to the Americas in late 2013. Besides CHIKV, other alphaviruses, such as the Ross River virus (RRV), Mayaro virus (MAYV), and Venezuelan equine encephalitis virus (VEEV), have emerged and have become a serious public health concern in recent years. Infections with the Old World alphaviruses (e.g., CHIKV, RRV) are primarily associated with polyarthritis and myalgia that can persist for months to years. On the other hand, New World alphaviruses such as VEEV cause mainly neurological disease. Despite the worldwide (re-)emergence of these viruses, there are no antivirals or vaccines available for the treatment or prevention of infections with alphaviruses. It is therefore of utmost importance to develop antiviral strategies against these viruses. We here provided an overview of the reported antiviral strategies against arthritogenic alphaviruses. In addition, we highlighted the future perspectives for the development and the proper use of such antivirals.

Repurposing Drugs for Mayaro Virus: Identification of EIDD-1931, Favipiravir and Suramin as Mayaro Virus Inhibitors

“…These compounds were originally used against other viruses: EIDD-1931 was developed to treat influenza [ 48 ], but is also active against SARS-CoV-2 infection, for which it is tested in clinical trials (phase II/III) [ 49 ]. Favipiravir is an influenza drug that has been approved in Japan for the treatment of pandemic influenza virus [ 50 ], and suramin is used for the treatment of African sleeping sickness and river blindness [ 51 ]. Favipiravir and suramin showed only modest activity against MAYV (EC 50 values of 79 µM and 124 µM, respectively), whereas EIDD-1931 was found to be a potent inhibitor with an EC 50 value of 1.6 µM.…”

Intracellular mono-ADP-ribosyltransferases at the host–virus interphase

“…Processing of the non-structural polyprotein of alphaviruses is dependent on the protease encoded by nsP2, an important target for antiviral drugs [ 229 , 230 ]. For CHIKV the protease is necessary for replication [ 107 , 231 ].…”

Antiviral strategies targeting host factors and mechanisms obliging +ssRNA viral pathogens

“… 195 Inhibition of de novo pyrimidine synthesis also occurs through an antiparasitic drug called atovaquone and has been shown to inhibit replication in CHIKV via dose dependent manner. 106 …”