Emetine inhibits replication of RNA and DNA viruses without generating drug-resistant virus variants

Khandelwal, Nitin; Chander, Yogesh; Rawat, Krishan Dutt; Riyesh, Thachamvally; Nishanth, Chikkahonnaiah; Sharma, Shalini; Jindal, Naresh; Tripathi, Bhupendra Nath; Barua, Sanjay; Kumar, Naveen

doi:10.1016/j.antiviral.2017.06.006

Cited by 75 publications

(85 citation statements)

References 25 publications

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“…However, its potential cardiotoxicity has restricted its clinical use in the recent years. It was found to process antiviral activity against a broad range of RNA and DNA viruses, including Zika virus, Ebolavirus, Cytomegalovirus, rabies virus, HIV-1, echovirus 1, buffalo poxvirus, bovine herpesvirus 1, peste des petits ruminants virus, Newcastle disease virus, herpes simplex virus-2, metapneumovirus, Rift Valley fever virus, and influenza (Andersen et al, 2019;Chaves Valadao et al, 2015;Khandelwal et al, 2017;MacGibeny et al, 2018;Mukhopadhyay et al, 2016;Yang et al, 2018). Emetine was also identified to inhibit hCoV-OC43, hCoV-NL43, SARS-CoV, MERS-CoV, and MHV-A59 in vitro with EC 50 reported at low micromolar range (Dyall et al, 2014;Shen et al, 2019).…”

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confidence: 99%

Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro

et al. 2020

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An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.

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confidence: 99%

Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro

et al. 2020

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“…Virus step-specific assays viz; attachment, entry, RNA synthesis, subcellular localization of viral proteins and budding were conducted as per the previously described methods (24). Thapsigargin was not found to affect virus attachment, RNA synthesis and budding (data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…SERCA2 ATPase Antibody (MA3-919) was procured from Invitrogen, (Carlsbad, USA). Anti-PPRV and anti-NDV serum is described elsewhere by our group (24). Secondary fluorescein isothiocyanate-conjugated anti-rabbit antibody and secondary Rhodamine-conjugated anti-mouse antibody were purchased from Sigma (Steinheim, Germany).…”

Section: Methodsmentioning

confidence: 99%

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Inhibitor of sarco/endoplasmic reticulum calcium-ATPase impairs paramyxovirus replication

Kumar

Barua

Tripathi

et al. 2018

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21Sarco/endoplasmic reticulum calcium-ATPase (SERCA) is a membrane bound 22 cytosolic enzyme that is known to regulate the uptake of calcium into the 23 sarco/endoplasmic reticulum. Herein, we demonstrate for the first time that SERCA can 24 also regulate paramyxovirus [Peste des petits ruminants virus (PPRV) and Newcastle 25 disease virus (NDV)] replication. Treatment of Vero cells with SERCA specific 26 inhibitor (Thapsigargin) at a concentration that is nontoxic to the cells significantly 27 reduced virus replication. Conversely, overexpression of SERCA rescued the inhibitory 28 effect of Thapsigargin on virus replication. PPRV/NDV infection induced SERCA 29 expression in Vero cells which could be blocked by Thapsigargin. With the help of 30 time-of-addition and virus step-specific assays, it was observed that Thapsigargin 31 specifically inhibits viral entry and subcellular localization of the viral proteins. 32

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“…Madin-Darby bovine kidney (MDBK) cells were grown in Dulbecco’s Modified Eagle’s Medium (DMEM) supplemented with antibiotics and 10% fetal calf serum. Reference BHV1 (VTCCAVA14) was available in our repository at National Centre for Veterinary Type Cultures (NCVTC), Hisar, India which has been described elsewhere [17,18].…”

Section: Methodsmentioning

confidence: 99%

Isolation and characterization of bovine herpes virus 5 (BHV5) from cattle in India

Kumar

Chander

Riyesh

et al. 2020

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15Bovine herpesvirus 1 (BHV1) and 5 (BHV5) are genetically and antigenically related 16 alphaherpesviruses. Infection with one virus induces protective immunity against the other. 17However, disease associated with BHV1 and BHV5 varies significantly; whereas BHV1 18 infection is usually associated with rhinotracheitis and abortion, BHV5 causes encephalitis in 19 cattle. BHV5 outbreaks are sporadic and mainly restricted to the South American countries. 20 We report BHV5 infection for the first time from aborted cattle in India. Based on the 21 characteristic cytopathic effects in MDBK cells, amplification of the viral genome in PCR, 22 differential PCR for BHV1/BHV5, nucleotide sequencing and restriction endonuclease 23 patterns, identity of the virus was confirmed as BHV5 subtype A. Serum samples from the 24 aborted cattle strongly neutralized both BHV1 and BHV5 suggesting an active viral infection 25 in the herd. Upon UL27, UL44 and UL54 gene-based sequence and phylogenetic analysis, the 26 isolated virus clustered with BHV5 strains and showed highest similarity with the Brazilian 27 BHV5 strains. 28 Author Summary 29BHV5 causes fatal meningoencephalitis that may result in a mortality rate of up to 100% in 30 cattle. BHV5 is rarely associated with abortion and its distribution is restricted to South 31 American countries. Only a few cases of this disease have been reported from other countries. 32For the first time, we provide a strong evidence of BHV5 infection from aborted cattle in 33 India. The finding may necessitate inclusion of BHV5 test protocol in testing of semen for 34 sexually transmitted diseases. Also, the isolated virus would be useful for developing 35 diagnostic, prophylactic and therapeutic agents to combat BHV5 disease in the country. 3 37 Introduction 38 Bovine herpesvirus types 1 (BHV1) and 5 (BHV5) belong to the family Herpesviridae, 39 subfamily Alphaherpesvirinae and genus varicellovirus [1]. They are genetically and 40 antigenically closely related and share ~85% nucleotide identity. BHV1 is prevalent globally 41 and causes infectious bovine rhinotracheitis (IBR) in cattle which is characterized by 42 conjunctivitis, rhinotracheitis, balanopostitis, infectious pustular vulvovaginitis, enteritis, 43 abortion and sometimes encephalitis. BHV1 infection results in considerable economic losses 44 due to decreased milk production, weight loss and abortions. 45 BHV5 usually infects young calves and mortality can causes up to 100% [2]. BHV5 46 mainly causes fatal meningoencephalitis in cattle and establishes latency in trigeminal 47 ganglion. The virus is excreted in nasal, ocular and genital secretions upon reactivation 48 (under stress). The clinical signs in affected cattle include depression, anorexia, weakness 49 followed by neurological signs, such as incoordination, muscular tremor, blindness, circling, 50 recumbency, head pressing, convulsions, paddling and death [3]. Occasionally, BHV5 has 51 been shown to be associated with the reproductive disorders [4]. 52 Herpesvirus ass...

show abstract

Emetine inhibits replication of RNA and DNA viruses without generating drug-resistant virus variants

Cited by 75 publications

References 25 publications

Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro

Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro

Inhibitor of sarco/endoplasmic reticulum calcium-ATPase impairs paramyxovirus replication

Isolation and characterization of bovine herpes virus 5 (BHV5) from cattle in India

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