Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents
Mody et al.
, Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents
, Communications Biology, doi:10.1038/s42003-020-01577-x (In Vitro)
Computational molecular modeling screening and in vitro
analysis for inhibitory effects on SARS-CoV-2 specific 3CLpro
enzyme, showing that ivermectin blocked more than 85% of 3CLpro
activity of SARS-CoV-2. Antiviral activity of ivermectin mediated through the blocking of α/β1 importin has been previously established, this analysis suggests an additional antiviral mechanism of ivermectin for SARS-CoV-2 via inhibitory effects on 3CLpro
.15 In Vitro studies
support the efficacy of ivermectin [Boschi, Caly, Croci, De Forni, Delandre, Jeffreys, Jitobaom, Jitobaom (B), Li, Liu, Mody, Mountain Valley MD, Segatori, Surnar, Yesilbag]
Mody et al., 20 Jan 2021, peer-reviewed, 9 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
Identiﬁcation of 3-chymotrypsin like protease
(3CLPro) inhibitors as potential anti-SARS-CoV-2
Vicky Mody1,3, Joanna Ho1, Savannah Wills1, Ahmed Mawri1, Latasha Lawson1, Maximilian C. C. J. C. Ebert2,
Guillaume M. Fortin2, Srujana Rayalam1 & Shashidharamurthy Taval 1,3 ✉
Emerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)
infection is a major threat to public health. The morbidity is increasing due to lack of SARSCoV-2 speciﬁc drugs. Herein, we have identiﬁed potential drugs that target the 3chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of
SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved
drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 speciﬁc
3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic
activity. The 100 ns molecular dynamics simulation studies showed that ivermectin may
require homodimeric form of 3CLpro enzyme for its inhibitory activity. In summary, these
molecules could be useful to develop highly speciﬁc therapeutically viable drugs to inhibit the
SARS-CoV-2 replication either alone or in combination with drugs speciﬁc for other SARSCoV-2 viral targets.
of Pharmaceutical Sciences, School of Pharmacy, Philadelphia College of Osteopathic Medicine – Georgia Campus, Suwanee, GA, USA.
Computing Group, 910-1010 Sherbrooke W, Montreal, QC H3A 2R7, Canada. 3These authors contributed equally: Vicky Mody,
Shashidharamurthy Taval. ✉email: email@example.com
COMMUNICATIONS BIOLOGY | (2021)4:93 | https://doi.org/10.1038/s42003-020-01577-x | www.nature.com/commsbio
COMMUNICATIONS BIOLOGY | https://doi.org/10.1038/s42003-020-01577-x
he major pandemic outbreak of the 21st century due to
severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) has become a global threat to public health because
of its high rate of infection leading to mortality. As of 24
December 2020, there are a total of 13,881,620 COVID-19 positive cases and 272,820 deaths in the United States alone and
64,326,880 conﬁrmed cases and 1,488,992 deaths globally (https://
coronavirus.jhu.edu/). The death toll is increasing at an alarming
rate because of the lack of COVID-19 speciﬁc drugs or vaccines.
Development, validation, and approval of COVID-19 speciﬁc
drugs takes years1. Therefore, the idea of drug repositioning, also
known as repurposing, is an important strategy to control the
sudden outbreak of life-threatening infectious agents that spread
rapidly. FDA approved anti-viral drugs are known to be safe for
use in humans2, but their effectiveness against SARS-CoV-2
needs to be experimentally validated. Several FDA approved antiviral drugs such as favipiravir, danoprevir, darunavir, lopinavir,
oseltamivir, ritonavir, remdesivir, and umifenovir are in clinical
trials to study anti-COVID-19 activity3. However, the effectiveness of these drugs for preventing or reducing the severity of
symptoms of COVID-19 has not yet been completely established.
Therefore, there is an urgent need to identify additional drug
candidates to target different SARS-CoV-2 proteins for enhanced
efﬁcacy in the treatment of COVID-19.
Recently, Wu et al.4 sequenced and compared SARS-CoV-2
genome with other..
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