Coronaviruses (CoVs) are a group of viruses from the family Coronaviridae that can infect humans and animals, causing mild to severe diseases. The ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a global threat, urging the development of new therapeutic strategies. Here we present a selection of relevant compounds that have been described from 2005 until now as having in vitro and/or in vivo antiviral activities against human and/or animal CoVs. We also present compounds that have reached clinical trials as well as further discussing the potentiality of other molecules for application in (re)emergent CoVs outbreaks. Finally, through rationalization of the data presented herein, we wish to encourage further research encompassing these compounds as potential SARS-CoV-2 drug candidates.

Despite a significative classical literature, metallodrugs have struggled to reach clinical practice. In light of the COVID-19 outbreak, this review aims at further encouraging and promoting the development of metallodrugs as viable antiviral agents.

Hepatitis C virus (HCV) is one of the leading causes of liver diseases and transplantation worldwide. The current available therapy for HCV infection is based on interferon-α, ribavirin and the new direct-acting antivirals (DAAs), such as NS3 protease and NS5B polymerase inhibitors. However, the high costs of drug design, severe side effects and HCV resistance presented by the existing treatments demonstrate the need for developing more efficient anti-HCV agents. This study aimed to evaluate the antiviral effects of sorbifolin (1) and pedalitin (2), two flavonoids fromPterogyne nitenson the HCV replication cycle. These compounds were investigated for their anti-HCV activities using genotype 2a JFH-1 subgenomic replicons and infectious virus systems. Flavonoids1and2inhibited virus entry up to 45.0% and 78.7% respectively at non-cytotoxic concentrations. The mechanism of the flavonoid2block to virus entry was demonstrated to be by both the direct action on virus particles and the interference on the host cells. Alternatively, the flavonoid1activity was restricted to its virucidal effect. Additionally, no inhibitory effects on HCV replication and release were observed by treating cells with these flavonoids. These data are the first description of1and2possessingin vitroanti-HCV activity.

Chikungunya virus (CHIKV) is the etiologic agent of Chikungunya fever, a globally spreading mosquito-borne disease. There is no approved antiviral or vaccine against CHIKV, highlighting an urgent need for novel therapies. In this context, snake venom proteins have demonstrated antiviral activity against several viruses, including arboviruses which are relevant to public health. In particular, the phospholipase A2_CB (PLA2_CB), a protein isolated from the venom of Crotalus durissus terrificus was previously shown to possess anti-inflammatory, antiparasitic, antibacterial and antiviral activities. In this study, we investigated the multiple effects of PLA2_CB on the CHIKV replicative cycle in BHK-21 cells using CHIKV-nanoluc, a marker virus carrying nanoluciferase reporter. The results demonstrated that PLA2_CB possess a strong anti-CHIKV activity with a selectivity index of 128. We identified that PLA2_CB treatment protected cells against CHIKV infection, strongly impairing virus entry by reducing adsorption and post-attachment stages. Moreover, PLA2_CB presented a modest yet significant activity towards post-entry stages of CHIKV replicative cycle. Molecular docking calculations indicated that PLA2_CB may interact with CHIKV glycoproteins, mainly with E1 through hydrophobic interactions. In addition, infrared spectroscopy measurements indicated interactions of PLA2_CB and CHIKV glycoproteins, corroborating with data from in silico analyses. Collectively, this data demonstrated the multiple antiviral effects of PLA2_CB on the CHIKV replicative cycle, and suggest that PLA2_CB interacts with CHIKV glycoproteins and that this interaction blocks binding of CHIKV virions to the host cells.

The worldwide outbreaks of the chikungunya virus (CHIKV) in the last years demonstrated the need for studies to screen antivirals against CHIKV. The virus was first isolated in Tanzania in 1952 and was responsible for outbreaks in Africa and Southwest Asia in subsequent years. Between 2007 and 2014, some cases were documented in Europe and America. The infection is associated with low rates of death; however, it can progress to a chronic disease characterized by severe arthralgias in infected patients. This infection is also associated with Guillain–Barré syndrome. There is no specific antivirus against CHIKV. Treatment of infected patients is palliative and based on analgesics and non-steroidal anti-inflammatory drugs to reduce arthralgias. Several natural molecules have been described as antiviruses against viruses such as dengue, yellow fever, hepatitis C, and influenza. This review aims to summarize the natural compounds that have demonstrated antiviral activity against chikungunya virus in vitro.

The Zika fever is an arboviral disease resulting from the infection with Zika virus (ZIKV). The virus is transmitted to humans by the bite of Aedes mosquitos, mainly Aedes aegypti and Aedes albopictus. ZIKV has been detected for decades in African and Asian regions and, since 2007, has spread to other continents; among them, infections are most reported in the Americas. This can be explained by the presence of vectors in highly populated and tropical regions where people are susceptible to contamination. ZIKV has been considered by the World Health Organization a serious public health problem because of the increasing number of cases of congenital malformation and neurological disorders related to its infection, such as microcephaly, Guillain–Barré syndrome, meningoencephalitis, and myelitis. There is no vaccine or specific antiviral against ZIKV. The infection is best prevented by avoiding mosquito bite, and the treatment of infected patients is palliative. In this context, the search for efficient antivirals is necessary but remains challenging. Here, we aim to review the molecules that have been described to interfere with ZIKV life cycle and discuss their potential use in ZIKV therapy.