Recent Drug Development and Medicinal Chemistry Approaches for the Treatment of SARS‐CoV‐2 Infection and COVID‐19

SARS-CoV-2 Omicron variant is highly sensitive to molnupiravir, nirmatrelvir, and the combination

(2022) Pengfei Li et al.   CELL RESEARCH

Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19

(2022) Jennifer Hammond et al.   NEW ENGLAND JOURNAL OF MEDICINE

Animal alphacoronaviruses found in human patients with acute respiratory illness in different countries.

(2022) Anastasia N. Vlasova et al.   Emerging Microbes & Infections

Discovery of S-217622, a Noncovalent Oral SARS-CoV-2 3CL Protease Inhibitor Clinical Candidate for Treating COVID-19

(2022) Yuto Unoh et al.   JOURNAL OF MEDICINAL CHEMISTRY

Potent Inhibition of SARS-CoV-2 nsp14 N7-Methyltransferase by Sulfonamide-Based Bisubstrate Analogues

(2022) Rostom Ahmed-Belkacem et al.   JOURNAL OF MEDICINAL CHEMISTRY

S-217622, a 3CL Protease Inhibitor and Clinical Candidate for SARS-CoV-2

(2022) Joel D. A. Tyndall   JOURNAL OF MEDICINAL CHEMISTRY

Drug Repurposing for COVID-19: A Review and a Novel Strategy to Identify New Targets and Potential Drug Candidates

(2022) Liliana Rodrigues et al.   MOLECULES

Covalent narlaprevir- and boceprevir-derived hybrid inhibitors of SARS-CoV-2 main protease

(2022) Daniel W. Kneller et al.   Nature Communications

Crystallization of Feline Coronavirus Mpro With GC376 Reveals Mechanism of Inhibition

(2022) Jimmy Lu et al.   Frontiers in Chemistry

An orally available Mpro inhibitor is effective against wild-type SARS-CoV-2 and variants including Omicron

(2022) Bao-Xue Quan et al.   Nature Microbiology

Small-Molecule Thioesters as SARS-CoV-2 Main Protease Inhibitors: Enzyme Inhibition, Structure–Activity Relationships, Antiviral Activity, and X-ray Structure Determination

(2022) Thanigaimalai Pillaiyar et al.   JOURNAL OF MEDICINAL CHEMISTRY

A multi-pronged evaluation of aldehyde-based tripeptidyl main protease inhibitors as SARS-CoV-2 antivirals

(2022) Yuying Ma et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

A systematic exploration of boceprevir-based main protease inhibitors as SARS-CoV-2 antivirals

(2022) Yugendar R. Alugubelli et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery

(2021) Ziyang Fu et al.   Nature Communications

Mechanism of SARS-CoV-2 polymerase stalling by remdesivir

(2021) Goran Kokic et al.   Nature Communications

Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

(2021) Vicky Mody et al.   Communications Biology

Targeting the Main Protease of SARS‐CoV‐2: From the Establishment of High Throughput Screening to the Design of Tailored Inhibitors

(2021) Julian Breidenbach et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Structure of the SARS-CoV-2 RNA-dependent RNA polymerase in the presence of favipiravir-RTP

(2021) Katerina Naydenova et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

SARS-CoV-2 Mpro inhibitors with antiviral activity in a transgenic mouse model

(2021) Jingxin Qiao et al.   SCIENCE

A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication

(2021) Shin-ichiro Hattori et al.   Nature Communications

Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors

(2021) Jerzy Osipiuk et al.   Nature Communications

Potent Noncovalent Inhibitors of the Main Protease of SARS-CoV-2 from Molecular Sculpting of the Drug Perampanel Guided by Free Energy Perturbation Calculations

(2021) Chun-Hui Zhang et al.   ACS Central Science

Corilagin inhibits SARS-CoV-2 replication by targeting viral RNA-dependent RNA polymerase

(2021) Quanjie Li et al.   Acta Pharmaceutica Sinica B

Expedited Approach toward the Rational Design of Noncovalent SARS-CoV-2 Main Protease Inhibitors

(2021) Naoya Kitamura et al.   JOURNAL OF MEDICINAL CHEMISTRY

Viral Proteases as Targets for COVID-19 Drug Development

(2021) Wei Zhu et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Small-Molecule Inhibitors of the Coronavirus Spike: ACE2 Protein–Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2

(2021) Damir Bojadzic et al.   ACS Infectious Diseases

Virtual Screening and Molecular Docking Studies for Discovery of Potential RNA-Dependent RNA Polymerase Inhibitors

(2021) Mohammed Y. Ghazwani et al.   Crystals

Baicalein and Baicalin Inhibit SARS-CoV-2 RNA-Dependent-RNA Polymerase

(2021) Keivan Zandi et al.   Microorganisms

Use of Janus kinase inhibitors in COVID-19: a prospective observational series in 522 individuals

(2021) Oleg Melikhov et al.   ANNALS OF THE RHEUMATIC DISEASES

A cell-based assay to discover inhibitors of SARS-CoV-2 RNA dependent RNA polymerase

(2021) Jianyuan Zhao et al.   ANTIVIRAL RESEARCH

Novel Canine Coronavirus Isolated from a Hospitalized Pneumonia Patient, East Malaysia

(2021) Anastasia N Vlasova et al.   CLINICAL INFECTIOUS DISEASES

Structure-Based Optimization of ML300-Derived, Noncovalent Inhibitors Targeting the Severe Acute Respiratory Syndrome Coronavirus 3CL Protease (SARS-CoV-2 3CLpro)

(2021) Sang Hoon Han et al.   JOURNAL OF MEDICINAL CHEMISTRY

Indole Chloropyridinyl Ester-Derived SARS-CoV-2 3CLpro Inhibitors: Enzyme Inhibition, Antiviral Efficacy, Structure–Activity Relationship, and X-ray Structural Studies

(2021) Arun K. Ghosh et al.   JOURNAL OF MEDICINAL CHEMISTRY

Peptidomimetic α-Acyloxymethylketone Warheads with Six-Membered Lactam P1 Glutamine Mimic: SARS-CoV-2 3CL Protease Inhibition, Coronavirus Antiviral Activity, and in Vitro Biological Stability

(2021) Bing Bai et al.   JOURNAL OF MEDICINAL CHEMISTRY

Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis

(2021) Florian Kabinger et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Allosteric Activation of SARS-CoV-2 RNA-Dependent RNA Polymerase by Remdesivir Triphosphate and Other Phosphorylated Nucleotides

(2021) Bing Wang et al.   mBio

Potent SARS-CoV-2 mRNA Cap Methyltransferase Inhibitors by Bioisosteric Replacement of Methionine in SAM Cosubstrate

(2021) Olga Bobiļeva et al.   ACS Medicinal Chemistry Letters

Discovery of Small Molecule Entry Inhibitors Targeting the Fusion Peptide of SARS-CoV-2 Spike Protein

(2021) Xin Hu et al.   ACS Medicinal Chemistry Letters

Identification of pyrogallol as a warhead in design of covalent inhibitors for the SARS-CoV-2 3CL protease

(2021) Haixia Su et al.   Nature Communications

The Structure-Based Design of SARS-CoV-2 nsp14 Methyltransferase Ligands Yields Nanomolar Inhibitors

(2021) Tomáš Otava et al.   ACS Infectious Diseases

Inhibitors of L-Type Calcium Channels Show Therapeutic Potential for Treating SARS-CoV-2 Infections by Preventing Virus Entry and Spread

(2021) Marco R. Straus et al.   ACS Infectious Diseases

Remdesivir Versus Standard-of-Care for Severe Coronavirus Disease 2019 Infection: An Analysis of 28-Day Mortality

(2021) Susan A Olender et al.   Open Forum Infectious Diseases

Improved SARS-CoV-2 Mpro inhibitors based on feline antiviral drug GC376: Structural enhancements, increased solubility, and micellar studies

(2021) Wayne Vuong et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

A Review of the Current Landscape of SARS-CoV-2 Main Protease Inhibitors: Have We Hit the Bullseye Yet?

(2021) Guillem Macip et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Design of SARS-CoV-2 PLpro Inhibitors for COVID-19 Antiviral Therapy Leveraging Binding Cooperativity

(2021) Zhengnan Shen et al.   JOURNAL OF MEDICINAL CHEMISTRY

COVID-19 Drug Development

(2021) Seungtaek Kim   JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY

Discovery of Di- and Trihaloacetamides as Covalent SARS-CoV-2 Main Protease Inhibitors with High Target Specificity

(2021) Chunlong Ma et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Chloropyridinyl Esters of Nonsteroidal Anti-Inflammatory Agents and Related Derivatives as Potent SARS-CoV-2 3CL Protease Inhibitors

(2021) Arun K. Ghosh et al.   MOLECULES

Discovery, Development, and Patent Trends on Molnupiravir: A Prospective Oral Treatment for COVID-19

(2021) Mohd. Imran et al.   MOLECULES

Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients

(2021) Angélica Jayk Bernal et al.   NEW ENGLAND JOURNAL OF MEDICINE

Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients

(2021) Robert L. Gottlieb et al.   NEW ENGLAND JOURNAL OF MEDICINE

An oral SARS-CoV-2 M pro inhibitor clinical candidate for the treatment of COVID-19

(2021) Dafydd R. Owen et al.   SCIENCE

Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors

(2021) Dmitriy Shcherbakov et al.   ACS Medicinal Chemistry Letters

Oral prodrug of remdesivir parent GS-441524 is efficacious against SARS-CoV-2 in ferrets

(2021) Robert M. Cox et al.   Nature Communications

Covid-19: UK becomes first country to authorise antiviral molnupiravir

(2021) Elisabeth Mahase   BMJ-British Medical Journal

Crystal structure of SARS-CoV-2 main protease in complex with protease inhibitor PF-07321332

(2021) Yao Zhao et al.   Protein & Cell

Baricitinib as potential treatment for 2019-nCoV acute respiratory disease

(2020) Peter Richardson et al.   LANCET

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

(2020) Chaolin Huang et al.   LANCET

A new coronavirus associated with human respiratory disease in China

(2020) Fan Wu et al.   NATURE

A pneumonia outbreak associated with a new coronavirus of probable bat origin

(2020) Peng Zhou et al.   NATURE

Drug Development and Medicinal Chemistry Efforts toward SARS‐Coronavirus and Covid‐19 Therapeutics

(2020) Arun K. Ghosh et al.   ChemMedChem

The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China

(2020) Wen Zhang et al.   CLINICAL IMMUNOLOGY

Drug repositioning is an alternative for the treatment of coronavirus COVID-19

(2020) Marissa B. Serafin et al.   INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS

Remdesivir for 5 or 10 Days in Patients with Severe Covid-19

(2020) Jason D. Goldman et al.   NEW ENGLAND JOURNAL OF MEDICINE

Remdesivir for the Treatment of Covid-19 — Preliminary Report

(2020) John H. Beigel et al.   NEW ENGLAND JOURNAL OF MEDICINE

Compassionate Use of Remdesivir for Patients with Severe Covid-19

(2020) Jonathan Grein et al.   NEW ENGLAND JOURNAL OF MEDICINE

Comprehensive Insights into the Catalytic Mechanism of Middle East Respiratory Syndrome 3C-Like Protease and Severe Acute Respiratory Syndrome 3C-Like Protease

(2020) Hao Wang et al.   ACS Catalysis

Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19

(2020) Richard T. Eastman et al.   ACS Central Science

Chemistry and Biology of SARS-CoV-2

(2020) Alexander Dömling et al.   Chem

Boceprevir, GC-376, and calpain inhibitors II, XII inhibit SARS-CoV-2 viral replication by targeting the viral main protease

(2020) Chunlong Ma et al.   CELL RESEARCH

[Comment] The COVID‑19 pandemic as a scientific and social challenge in the 21st century

(2020) Vassilios Zoumpourlis et al.   Molecular Medicine Reports

Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity

(2020) Donghyuk Shin et al.   NATURE

Structural analysis of the SARS-CoV-2 methyltransferase complex involved in RNA cap creation bound to sinefungin

(2020) Petra Krafcikova et al.   Nature Communications

Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19

(2020) Christoph D. Spinner et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19

(2020) Robert L. Hoffman et al.   JOURNAL OF MEDICINAL CHEMISTRY

High-resolution structures of the SARS-CoV-2 2′-O-methyltransferase reveal strategies for structure-based inhibitor design

(2020) Monica Rosas-Lemus et al.   Science Signaling

Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease

(2020) Lifeng Fu et al.   Nature Communications

Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis

(2020) Ashleigh Shannon et al.   Nature Communications

Crystal structure of SARS-CoV-2 papain-like protease

(2020) Xiaopan Gao et al.   Acta Pharmaceutica Sinica B

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19

(2020) Andre C. Kalil et al.   NEW ENGLAND JOURNAL OF MEDICINE

Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase

(2019) Ariane J. Brown et al.   ANTIVIRAL RESEARCH

Origin and evolution of pathogenic coronaviruses

(2018) Jie Cui et al.   NATURE REVIEWS MICROBIOLOGY

Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis

(2017) Niels C Pedersen et al.   JOURNAL OF FELINE MEDICINE AND SURGERY

The aminopeptidase inhibitor, z-L-CMK, is toxic and induces cell death in Jurkat T cells through oxidative stress

(2017) E. H. Yeo et al.   TOXICOLOGY MECHANISMS AND METHODS

Molecular Evolution of Human Coronavirus Genomes

(2017) Diego Forni et al.   TRENDS IN MICROBIOLOGY

The aminopeptidase inhibitor, z-L-CMK, is toxic and induces cell death in Jurkat T cells through oxidative stress

(2017) E. H. Yeo et al.   TOXICOLOGY MECHANISMS AND METHODS

An Overview of Severe Acute Respiratory Syndrome–Coronavirus (SARS-CoV) 3CL Protease Inhibitors: Peptidomimetics and Small Molecule Chemotherapy

(2016) Thanigaimalai Pillaiyar et al.   JOURNAL OF MEDICINAL CHEMISTRY

The SARS-coronavirus papain-like protease: Structure, function and inhibition by designed antiviral compounds

(2015) Yahira M. Báez-Santos et al.   ANTIVIRAL RESEARCH

Broad-Spectrum Inhibitors against 3C-Like Proteases of Feline Coronaviruses and Feline Caliciviruses

(2015) Yunjeong Kim et al.   JOURNAL OF VIROLOGY

Middle East respiratory syndrome

(2015) Alimuddin Zumla et al.   LANCET

South Korean MERS outbreak spotlights lack of research

(2015) Declan Butler   NATURE

Catalytic Function and Substrate Specificity of the Papain-Like Protease Domain of nsp3 from the Middle East Respiratory Syndrome Coronavirus

(2014) Y. M. Baez-Santos et al.   JOURNAL OF VIROLOGY

Structural Basis for the Ubiquitin-Linkage Specificity and deISGylating Activity of SARS-CoV Papain-Like Protease

(2014) Kiira Ratia et al.   PLoS Pathogens

From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses

(2013) Rolf Hilgenfeld et al.   ANTIVIRAL RESEARCH

In-vitro renal epithelial cell infection reveals a viral kidney tropism as a potential mechanism for acute renal failure during Middle East Respiratory Syndrome (MERS) Coronavirus infection

(2013) Isabella Eckerle et al.   Virology Journal

Discovery, Synthesis, And Structure-Based Optimization of a Series of N-(tert-Butyl)-2-(N-arylamido)-2-(pyridin-3-yl) Acetamides (ML188) as Potent Noncovalent Small Molecule Inhibitors of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) 3CL Protease

(2012) Jon Jacobs et al.   JOURNAL OF MEDICINAL CHEMISTRY

Broad-Spectrum Antivirals against 3C or 3C-Like Proteases of Picornaviruses, Noroviruses, and Coronaviruses

(2012) Y. Kim et al.   JOURNAL OF VIROLOGY

Structure-Based Design, Synthesis, and Biological Evaluation of a Series of Novel and Reversible Inhibitors for the Severe Acute Respiratory Syndrome−Coronavirus Papain-Like Protease

(2009) Arun K. Ghosh et al.   JOURNAL OF MEDICINAL CHEMISTRY

A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication

(2008) K. Ratia et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

SARS coronavirus replicase proteins in pathogenesis

(2007) Rachel L. Graham et al.   VIRUS RESEARCH