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.

Chikungunya virus (CHIKV) is a mosquito-transmitted virus of special concern as it causes Chikungunya fever, characterized by an acute febrile illness, rash, and arthralgia that can progress to chronic and debilitating arthritic symptoms. The effects of climate change on the geographic distribution of the mosquito vector has the potential to expose more of the globe to this virus. No antiviral agents or vaccines are currently available against CHIKV infection and the development of novel therapies that may lead to a future treatment is therefore necessary. In this context, the ADP-ribose binding site of the CHIKV nsP3 macro domain has been reported as a potential target for the development of antivirals. Mutations in the ADP-ribose binding site demonstrated decreased viral replication in cell culture and reduced virulence. In this study, 48,750 small molecules were screened in silico for their ability to bind to the ADP-ribose binding site of the CHIKV nsP3 macro domain. From this in silico analysis, 12 molecules were selected for in vitro analysis using a CHIKV subgenomic replicon in Huh-7 cells. Cell viability and CHIKV replication were evaluated and molecules C5 and C13 demonstrated 53 and 66% inhibition of CHIKV replication, respectively. By using a CHIKV-Dual luciferase replicon contain two reporter genes, we also demonstrated that the treatment with either compounds are probably interfering in the early replication rather than after RNA replication has occurred.

Considering our previous findings on the remarkable activity exhibited by cobalt(III) with 2-acetylpyridine-N(4)-R-thiosemicarbazone (Hatc-R) compounds against Mycobacterium tuberculosis, the present study aimed to explored new structure features of the complexes of the type [Co(atc--R)₂]Cl, where R = methyl (Me, 1) or phenyl (Ph, 2) (¹³C NMR, high-resolution mass spectrometry, LC–MS/MS, fragmentation study) together with its antibacterial and antiviral biological activities. The minimal inhibitory and minimal bactericidal concentrations (MIC and MBC) were determined, as well as the antiviral potential of the complexes on chikungunya virus (CHIKV) infection in vitro and cell viability. [Co(atc-Ph)₂]Cl revealed promising MIC and MBC values which ranged from 0.39 to 0.78 µg/mL in two strains tested and presented high potential against CHIKV by reducing viral replication by up to 80%. The results showed that the biological activity is strongly influenced by the peripheral substituent groups at the N(4) position of the atc-R¹⁻ ligands. In addition, molecular docking analysis was performed. The relative binding energy of the docked compound with five bacteria strains was found in the range of −3.45 and −9.55 kcal/mol. Thus, this work highlights the good potential of cobalt(III) complexes and provide support for future studies on this molecule aiming at its antibacterial and antiviral therapeutic application.

Chikungunya virus (CHIKV) and Zika virus (ZIKV) are important disease-causing agents worldwide. Currently, there are no antiviral drugs or vaccines approved to treat these viruses. However, peptides have shown great potential for new drug development. A recent study described (p-BthTX-I)₂K [(KKYRYHLKPF)₂K], a peptide derived from the Bothropstoxin-I toxin in the venom of the Bothrops jararacussu snake, showed antiviral activity against SARS-CoV-2. In this study, we assessed the activity of this peptide against CHIKV and ZIKV and its antiviral action in the different stages of the viral replication cycle in vitro. We observed that (p-BthTX-I)₂K impaired CHIKV infection by interfering with the early steps of the viral replication cycle, reducing CHIKV entry into BHK-21 cells specifically by reducing both the attachment and internalization steps. (p-BthTX-I)₂K also inhibited the ZIKV replicative cycle in Vero cells. The peptide protected the cells against ZIKV infection and decreased the levels of the viral RNA and the NS3 protein of this virus at viral post-entry steps. In conclusion, this study highlights the potential of the (p-BthTX-I)₂K peptide to be a novel broad-spectrum antiviral candidate that targets different steps of the replication cycle of both CHIKV and ZIKV.