Drug-Like Small Molecule Inhibitors of Viral Targets

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Pharmaceutical Science".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 3175

Special Issue Editors

Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA
Interests: drug-likeness evaluation; ADME/PK; drug discovery
Translational Medicine R&D Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
Interests: drug repurposing; antivirals; natural products; bone disease

Special Issue Information

Dear Colleagues,

The outbreak of the COVID-19 pandemic has stressed the urgent need to identify antiviral targets and develop therapeutics against emerging viruses, and the recent success of remdesivir, molnupiravir, and paxlovid has reaffirmed small-molecule inhibitors as a critical antiviral strategy. In early small-molecule drug discovery, drug likeness is an important concept used in the screening and selection of lead compounds that have higher probability of success in later development phase. Drug likeness is referred to as properties of compounds that may confer adequate ADME/pharmacokinetics (PKs) and acceptable toxicity profiles to survive throughout clinical trials.

In this Special Issue, we welcome original research articles, short communications, and reviews related to the discovery, synthesis, and optimization of small-molecule inhibitors against valid viral targets of emerging viruses, including but not limited to coronaviruses, flaviviruses, retroviruses, and herpesviruses. We particularly welcome papers involving studies, either in part or in whole, that seek to evaluate and optimize drug likeness of lead compounds using Lipinski's rule of five, in silico or in vitro ADMET prediction and profiling, multiparameter optimization approaches, PK/PD modeling, or physiologically based PK (PBPK). We also encourage the submission of papers related to new antiviral targets, new antiviral drug combinations, or drug repurposing.

We look forward to receiving your submissions!

Dr. Jiashu Xie
Dr. Yan Wang
Guest Editors

Manuscript Submission Information

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Keywords

  • emerging viruses
  • small-molecule inhibitors
  • antiviral
  • drug likeness
  • viral targets
  • drug discovery
  • ADME
  • PK
  • toxicity
  • drug combination
  • drug repurposing

Published Papers (2 papers)

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Research

14 pages, 1025 KiB  
Article
Design of 4-Substituted Sulfonamidobenzoic Acid Derivatives Targeting Coxsackievirus B3
by Anton A. Shetnev, Alexandrina S. Volobueva, Valeria A. Panova, Vladimir V. Zarubaev and Sergey V. Baykov
Life 2022, 12(11), 1832; https://doi.org/10.3390/life12111832 - 09 Nov 2022
Cited by 5 | Viewed by 1260
Abstract
A series of novel 4-substituted sulfonamidobenzoic acid derivatives was synthesized as the structural evolution of 4-(4-(1,3-dioxoisoindolin-2-yl)phenylsulfonamido)benzoic acid, which is the known inhibitor of the enterovirus life cycle. Antiviral properties of prepared compounds were evaluated in vitro using phenotypic screening and viral yield reduction [...] Read more.
A series of novel 4-substituted sulfonamidobenzoic acid derivatives was synthesized as the structural evolution of 4-(4-(1,3-dioxoisoindolin-2-yl)phenylsulfonamido)benzoic acid, which is the known inhibitor of the enterovirus life cycle. Antiviral properties of prepared compounds were evaluated in vitro using phenotypic screening and viral yield reduction assay. Their capsid binding properties were verified in thermostability assay. We identified two new hit-compounds (4 and 7a) with high activity against the coxsackievirus B3 (Nancy, CVB3) strain with potencies (IC50 values of 4.29 and 4.22 μM, respectively) which are slightly superior to the reference compound 2a (IC50 5.54 μM). Both hits changed the heat inactivation of CVB3 in vitro to higher temperatures, suggesting that they are capsid binders, as 2a is. The results obtained can serve as a basis for further development of the lead compounds for novel drug design to combat enterovirus infection. Full article
(This article belongs to the Special Issue Drug-Like Small Molecule Inhibitors of Viral Targets)
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12 pages, 2334 KiB  
Article
Glycyrrhizin Inhibits SARS-CoV-2 Entry into Cells by Targeting ACE2
by Ming-Feng He, Jian-Hui Liang, Yan-Ni Shen, Jin-Wen Zhang, Ying Liu, Kuang-Yang Yang, Li-Chu Liu, Junyi Wang, Qian Xie, Chun Hu, Xun Song and Yan Wang
Life 2022, 12(11), 1706; https://doi.org/10.3390/life12111706 - 26 Oct 2022
Cited by 4 | Viewed by 1405
Abstract
Coronavirus Disease 2019 (COVID-19) is a highly infectious and pathogenic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early in this epidemic, the herbal formulas used in traditional Chinese medicine (TCM) were widely used for the treatment of COVID-19 in [...] Read more.
Coronavirus Disease 2019 (COVID-19) is a highly infectious and pathogenic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early in this epidemic, the herbal formulas used in traditional Chinese medicine (TCM) were widely used for the treatment of COVID-19 in China. According to Venn diagram analysis, we found that Glycyrrhizae Radix et Rhizoma is a frequent herb in TCM formulas against COVID-19. The extract of Glycyrrhizae Radix et Rhizoma exhibits an anti-SARS-CoV-2 replication activity in vitro, but its pharmacological mechanism remains unclear. We here demonstrate that glycyrrhizin, the main active ingredient of Glycyrrhizae Radix et Rhizoma, prevents the coronavirus from entering cells by targeting angiotensin-converting enzyme 2 (ACE2). Glycyrrhizin inhibited the binding of the spike protein of the SARS-CoV-2 to ACE2 in our Western blot-based assay. The following bulk RNA-seq analysis showed that glycyrrhizin down-regulated ACE2 expression in vitro which was further confirmed by Western blot and quantitative PCR. Together, we believe that glycyrrhizin inhibits SARS-CoV-2 entry into cells by targeting ACE2. Full article
(This article belongs to the Special Issue Drug-Like Small Molecule Inhibitors of Viral Targets)
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