Antiviral activity of micafungin against enterovirus 71
Chonsaeng Kim, Hyunju Kang, Dong-eun Kim, Jae-Hyoung Song, Miri Choi, Mingu Kang, Kyungjin Lee, Hae Soo Kim, Jin Soo Shin, Hyejeong Jeong, Sunhee Jung, Sang-Bae Han, Jong Heon Kim, Hyun-Jeong Ko, Chong-Kyo Lee, Meehyein Kim & Sungchan Cho
Virology Journal volume 13, Article number: 99 (2016) Cite this article
Enterovirus 71 (EV71) is a major causative agent of hand-foot-mouth disease (HFMD) and also causes severe neurological complications, leading to fatality in young children. However, no effective therapy is currently available for the treatment of this infection.
We identified micafungin, an echinocandin antifungal drug, as a novel inhibitor of EV71. Micafungin potently inhibits the proliferation of EV71 as well as the replication of EV71 replicon in cells with a low micromolar IC50 (~5 μM). The strong antiviral effect of micafungin on EV71 replicon and the result from time-of-addition experiment demonstrated a targeting of micafungin on virion-independent intracellular process(es) during EV71 infection. Moreover, an extensive analysis excluded the involvement of 2C and 3A proteins, IRES-dependent translation, and also that of polyprotein processing in the antiviral effect of micafungin.
Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs
Sangeun Jeon, Meehyun Ko, Jihye Lee, Inhee Choi, Soo Young Byun, Soonju Park, David Shum, Seungtaek Kim
Antimicrobial Agents and Chemotherapy DOI: 10.1128/AAC.00819-20
Drug repositioning is the only feasible option to immediately address the COVID-19 global challenge. We screened a panel of 48 FDA-approved drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which were preselected by an assay of SARS-CoV. We identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low 50% inhibitory concentrations (IC50s), and in particular, two FDA-approved drugs—niclosamide and ciclesonide—were notable in some respects.
Micafungin is a novel anti-viral agent of chikungunya virus through multiple mechanisms
Yi-Jung Ho 1, Feng-Cheng Liu 2, Chia-Tsui Yeh 3, Chuen Mi Yang 3, Chang-Chi Lin 4, Te-Yu Lin 5, Po-Shiuan Hsieh 6, Ming-Kuan Hu 1, Zhiyuan Gong 7, Jeng-Wei Lu 8
Antiviral Res. 2018 Nov;159:134-142. doi: 10.1016/j.antiviral.2018.10.005. Epub 2018 Oct 6.
The chikungunya virus (CHIKV) is a mosquito-borne virus that belongs to the genus Alphavirus, family Togaviridae. It is the cause of chikungunya fever in humans, which presents a serious global threat due to its high rate of contagion. The clinical symptoms of CHIKV include fever and persistent, severe arthritis. Micafungin has broad-spectrum fungicidal activity against Candida spp. is a promising echinocandin that was recently approved by the U.S. Food and Drug Administration (FDA) and has demonstrated activity against Candida and Aspergillus. Recent studies have demonstrated the antiviral activity of micafungin; however, the inhibitory effects against CHIKV have yet to be investigated. Our objectives in this study were to explore the antiviral effects of micafungin on CHIKV infection and to elucidate the potential molecular mechanisms of inhibition. We determined that micafungin has the ability to counter CHIKV-induced cytopathic effects. We further discovered that micafungin limits virus replication, release, cell-to-cell transmission, and also slightly affected virus stability during high doses treatment. The efficacy of micafungin was further confirmed against two clinical isolates of CHIKV and two alphaviruses: Sindbis virus (SINV) and Semliki Forest virus (SFV). Our findings suggest that micafungin has considerable potential as a novel inhibitor against the viral replication, and intracellular and extracellular transmission of CHIKV, and has a little effect on virus stability. Our findings also suggest that micafungin could have curative effects on other alphavirus infections.
Suramin, Penciclovir and Anidulafungin bind nsp12, which governs the RNA-dependent-RNA polymerase activity of SARS-CoV-2, with higher interaction energy than Remdesivir, indicating potential in the treatment of Covid-19 infection
Preprint available April 2020
Sanjay Kumar Dey, Manisha Saini, Chetna Dhembla, Suman Kundu
A century back about 50 million lives were claimed by an influenza pandemic, the ‘Spanish Flu’, which had affected a quarter of the world’s population. Today, we are faced with another recrudescence, namely Covid-19, a highly infectious viral pneumonia that has already claimed more than 150,000 lives around the globe, for which no vaccine or therapeutic agents have yet been made available. A feasible, and quicker, method to resolve this problem forthwith would be ‘drug repositioning’. In this study, we investigated FDA-approved drugs based on their previously promising potential on similar diseases like SARS, MERS, Ebola, Hepatitis C and other viral diseases. Other selected classes of FDA and WHO-EML approved drugs like antimalarials, antibacterials and antifungals were also investigated based on their remote association to viral drug targets reported spuriously in literature. These drugs were docked onto the three-dimensional structure of nsp12 protein which reigns the RNA-dependent RNA polymerase activity of SARS-CoV-2 and is considered as one of the major therapeutic targets for coronaviruses. Suramin, Penciclovir and Anidulafungin were found to bind nsp12 with higher binding energies than Remdesivir, which has been reported for its potential in treating Covid-19 infected patients and is currently in clinical trials. A critical significance of anti-RNA-dependent-RNA polymerase drug candidates against SARS-CoV-2 within the pool of the FDA/WHO-EML approved drugs are expected to be helpful to battle the menace that has threatened the existence of humanity.