Targeting SARS-CoV-2 entry processes: The promising potential and future of host-targeted small-molecule inhibitors

Inhibition of PIKFYVE kinase interferes ESCRT pathway to suppress RNA virus replication

(2023) Zhen Luo et al.   JOURNAL OF MEDICAL VIROLOGY

Inhibition of Human Coronaviruses by Combinations of Host-Targeted and Direct-Acting Antivirals

(2023) Patricia de León et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Identification of Four New Chemical Series of Small Drug‐Like Natural Products as Potential Neuropilin‐1 Inhibitors by Structure‐Based Virtual Screening: Pharmacophore‐Based Molecular Docking and Dynamics Simulation

(2023) Abdellah Sabki et al.   CHEMISTRY & BIODIVERSITY

Antitarget, Anti-SARS-CoV-2 Leads, Drugs, and the Drug Discovery–Genetics Alliance Perspective

(2023) Cecilia Pozzi et al.   Journal of Medicinal Chemistry

Current thoughts on cellular functions of numb-associated kinases

(2023) Chenxi Huang et al.   MOLECULAR BIOLOGY REPORTS

Inhibition of ACE2‐Spike Interaction by an ACE2 Binder Suppresses SARS‐CoV‐2 Entry

(2022) Young‐Hee Shin et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Effect of an Inhibitor on the ACE2-Receptor-Binding Domain of SARS-CoV-2

(2022) Gaurav Sharma et al.   Journal of Chemical Information and Modeling

Brilacidin, a COVID‐19 drug candidate, demonstrates broad‐spectrum antiviral activity against human coronaviruses OC43, 229E, and NL63 through targeting both the virus and the host cell

(2022) Yanmei Hu et al.   JOURNAL OF MEDICAL VIROLOGY

Obatoclax inhibits SARS-CoV-2 entry by altered endosomal acidification and impaired cathepsin and furin activity in vitro

(2022) Binli Mao et al.   Emerging Microbes & Infections

Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo-controlled trial

(2022) E Wesley Ely et al.   Lancet Respiratory Medicine

Identification of potent small molecule inhibitors of SARS-CoV-2 entry

(2022) Sonia Mediouni et al.   SLAS Discovery

Dichlorophenylpyridine-Based Molecules Inhibit Furin through an Induced-Fit Mechanism

(2022) Sven O. Dahms et al.   ACS Chemical Biology

ADAM10 and ADAM17 promote SARS‐CoV‐2 cell entry and spike protein‐mediated lung cell fusion

(2022) Georg Jocher et al.   EMBO REPORTS

Heparanase Blockade as a Novel Dual-Targeting Therapy for COVID-19

(2022) Jingyu Xiang et al.   JOURNAL OF VIROLOGY

A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic

(2022) Tirosh Shapira et al.   NATURE

Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike–ACE2 Interaction

(2022) Scott E. Guimond et al.   ACS Central Science

Tuftsin: A Natural Molecule Against SARS-CoV-2 Infection

(2022) Jiahao Huang et al.   Frontiers in Molecular Biosciences

Dual Inhibition of Vacuolar-ATPase and TMPRSS2 Is Required for Complete Blockade of SARS-CoV-2 Entry into Cells

(2022) Simoun Icho et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Numb-associated kinases are required for SARS-CoV-2 infection and are cellular targets for antiviral strategies

(2022) Marwah Karim et al.   ANTIVIRAL RESEARCH

In vitro characterization of the furin inhibitor MI-1851: Albumin binding, interaction with cytochrome P450 enzymes and cytotoxicity

(2022) Erzsébet Pászti-Gere et al.   BIOMEDICINE & PHARMACOTHERAPY

Zinc pyrithione is a potent inhibitor of PLPro and cathepsin L enzymes with ex vivo inhibition of SARS-CoV-2 entry and replication

(2022) Jerneja Kladnik et al.   JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation

(2022) Bryan J. Fraser et al.   Nature Chemical Biology

Identification of potential COVID-19 treatment compounds which inhibit SARS Cov2 prototypic, Delta and Omicron variant infection

(2022) Prabhakaran Kumar et al.   VIROLOGY

Novel cleavage sites identified in SARS-CoV-2 spike protein reveal mechanism for cathepsin L-facilitated viral infection and treatment strategies

(2022) Miao-Miao Zhao et al.   Cell Discovery

Two-pore channel blockade by phosphoinositide kinase inhibitors YM201636 and PI-103 determined by a histidine residue near pore-entrance

(2022) Canwei Du et al.   Communications Biology

PIKfyve-specific inhibitors restrict replication of multiple coronaviruses in vitro but not in a murine model of COVID-19

(2022) James Logue et al.   Communications Biology

Expression profiles of respiratory V-ATPase and calprotectin in SARS-CoV-2 infection

(2022) Yapeng Hou et al.   Cell Death Discovery

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

(2022) Arun K. Ghosh et al.   ChemMedChem

Mechanism of N-0385 blocking SARS-CoV-2 to treat COVID-19 based on molecular docking and molecular dynamics

(2022) Jun-Feng Cao et al.   Frontiers in Microbiology

Targeting SARS-CoV-2 and host cell receptor interactions

(2022) Siew Pheng Lim   ANTIVIRAL RESEARCH

Phenothiazines inhibit SARS-CoV-2 cell entry via a blockade of spike protein binding to neuropilin-1

(2022) Mei Hashizume et al.   ANTIVIRAL RESEARCH

Hypothesis: Efficacy of early treatments with some NSAIDs in COVID‐19: Might it also depend on their direct and/or indirect zinc chelating ability?

(2022) Loris Zamai   BRITISH JOURNAL OF PHARMACOLOGY

Lysosomal ion channels involved in cellular entry and uncoating of enveloped viruses: Implications for therapeutic strategies against SARS-CoV-2

(2021) Zhuangzhuang Zhao et al.   CELL CALCIUM

AXL is a candidate receptor for SARS-CoV-2 that promotes infection of pulmonary and bronchial epithelial cells

(2021) Shuai Wang et al.   CELL RESEARCH

Domains and Functions of Spike Protein in SARS-Cov-2 in the Context of Vaccine Design

(2021) Xuhua Xia   Viruses-Basel

SARS-CoV-2 protein drug targets landscape: a potential pharmacological insight view for the new drug development

(2021) Chiranjib Chakraborty et al.   Expert Review of Clinical Pharmacology

Brilacidin Demonstrates Inhibition of SARS-CoV-2 in Cell Culture

(2021) Allison Bakovic et al.   Viruses-Basel

Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity

(2021) Markus Hoffmann et al.   EBioMedicine

Upregulation of the Renin–Angiotensin System Pathways and SARS-CoV-2 Infection: The Rationale for the Administration of Zinc-Chelating Agents in COVID-19 Patients

(2021) Loris Zamai   Cells

A Clinical-Stage Cysteine Protease Inhibitor blocks SARS-CoV-2 Infection of Human and Monkey Cells

(2021) Drake M. Mellott et al.   ACS Chemical Biology

Novel Compounds Targeting Neuropilin Receptor 1 with Potential To Interfere with SARS-CoV-2 Virus Entry

(2021) Samantha Perez-Miller et al.   ACS Chemical Neuroscience

Repurposing potential of Ayurvedic medicinal plants derived active principles against SARS-CoV-2 associated target proteins revealed by molecular docking, molecular dynamics and MM-PBSA studies

(2021) Akalesh Kumar Verma et al.   BIOMEDICINE & PHARMACOTHERAPY

SARS-CoV-2 entry inhibitors by dual targeting TMPRSS2 and ACE2: An in silico drug repurposing study

(2021) Krishnaprasad Baby et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Molecular basis of the new COVID-19 target neuropilin-1 in complex with SARS-CoV-2 S1 C-end rule peptide and small-molecule antagonists

(2021) Methus Klaewkla et al.   JOURNAL OF MOLECULAR LIQUIDS

Mechanism of Ligand Recognition by Human ACE2 Receptor

(2021) Apurba Bhattarai et al.   Journal of Physical Chemistry Letters

Milk Peptides as Novel Multi‐Targeted Therapeutic Candidates for SARS-CoV2

(2021) H. Pradeep et al.   PROTEIN JOURNAL

Molecular basis of V-ATPase inhibition by bafilomycin A1

(2021) Rong Wang et al.   Nature Communications

OFF-State-Specific Inhibition of the Proprotein Convertase Furin

(2021) Sven O. Dahms et al.   ACS Chemical Biology

Heparanase as a Potential Player in SARS-CoV-2 Infection and Induced-Coagulopathy

(2021) Safa Kinaneh et al.   BIOSCIENCE REPORTS

From Cancer to COVID‐19: A Perspective on Targeting Heparan Sulfate‐Protein Interactions

(2021) Mohit Chhabra et al.   CHEMICAL RECORD

Iterated Virtual Screening-Assisted Antiviral and Enzyme Inhibition Assays Reveal the Discovery of Novel Promising Anti-SARS-CoV-2 with Dual Activity

(2021) Rania Hamdy et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Targeting the glycans: A paradigm for host‐targeted and COVID‐19 drug design

(2021) Fatemeh Pourrajab   JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

Self-Masked Aldehyde Inhibitors: A Novel Strategy for Inhibiting Cysteine Proteases

(2021) Linfeng Li et al.   JOURNAL OF MEDICINAL CHEMISTRY

Host proviral and antiviral factors for SARS-CoV-2

(2021) Lu Lv et al.   VIRUS GENES

The TMPRSS2 Inhibitor Nafamostat Reduces SARS-CoV-2 Pulmonary Infection in Mouse Models of COVID-19

(2021) Kun Li et al.   mBio

Characterization of the Modulatory Effect of Hydroxychloroquine on ACE2 Activity: New Insights in relation to COVID-19

(2021) Juan E. Tichauer et al.   Biomed Research International

Cellular host factors for SARS-CoV-2 infection

(2021) Jim Baggen et al.   Nature Microbiology

Telaprevir is a potential drug for repurposing against SARS-CoV-2: computational and in vitro studies

(2021) Amal Mahmoud et al.   Heliyon

Which ones, when and why should renin-angiotensin system inhibitors work against COVID-19?

(2021) Mariele Montanari et al.   Advances in Biological Regulation

RdRp inhibitors and COVID-19: Is molnupiravir a good option?

(2021) Seyed Mohammad Reza Hashemian et al.   BIOMEDICINE & PHARMACOTHERAPY

Potential of turmeric-derived compounds against RNA‐dependent RNA polymerase of SARS‐CoV‐2: An in-silico approach

(2021) Rahul Singh et al.   COMPUTERS IN BIOLOGY AND MEDICINE

Structural and Biochemical Analysis of the Dual Inhibition of MG-132 against SARS-CoV-2 Main Protease (Mpro/3CLpro) and Human Cathepsin-L

(2021) Elisa Costanzi et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

In silico identification of SARS-CoV-2 cell entry inhibitors from selected natural antivirals

(2021) Yusuf Şimşek et al.   JOURNAL OF MOLECULAR GRAPHICS & MODELLING

Mechanisms of SARS-CoV-2 entry into cells

(2021) Cody B. Jackson et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells

(2021) Matthew Mahoney et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Mechanism of Microbial Metabolite Leupeptin in the Treatment of COVID-19 by Traditional Chinese Medicine Herbs

(2021) Lifeng Fu et al.   mBio

Epigenetic targeting of the ACE2 and NRP1 viral receptors limits SARS-CoV-2 infectivity

(2021) Maria Laura Saiz et al.   Clinical Epigenetics

A Review of Small Molecule Inhibitors and Functional Probes of Human Cathepsin L

(2020) Dibyendu Dana et al.   MOLECULES

Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs

(2020) Sangeun Jeon et al.   ANTIMICROBIAL AGENTS AND CHEMOTHERAPY

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

(2020) Alexandra C. Walls et al.   CELL

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

(2020) Markus Hoffmann et al.   CELL

Clinical Features of 69 Cases With Coronavirus Disease 2019 in Wuhan, China

(2020) Zhongliang Wang et al.   CLINICAL INFECTIOUS DISEASES

Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

(2020) Jun Lan et al.   NATURE

ACE2, the Receptor that Enables Infection by SARS‐CoV‐2: Biochemistry, Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators

(2020) Lissy Z. F. Gross et al.   ChemMedChem

Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2

(2020) Yuan-Lin Kang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Targeting Two-Pore Channels: Current Progress and Future Challenges

(2020) Xuhui Jin et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2

(2020) Thomas Mandel Clausen et al.   CELL

Insights into Lysosomal PI(3,5)P2 Homeostasis from a Structural-Biochemical Analysis of the PIKfyve Lipid Kinase Complex

(2020) Joshua A. Lees et al.   MOLECULAR CELL

NARINGENIN IS A POWERFUL INHIBITOR OF SARS-CoV-2 INFECTION IN VITRO

(2020) Nicola Clementi et al.   PHARMACOLOGICAL RESEARCH

Neuropilin-1 is a host factor for SARS-CoV-2 infection

(2020) James L. Daly et al.   SCIENCE

Furin Inhibitors Block SARS-CoV-2 Spike Protein Cleavage to Suppress Virus Production and Cytopathic Effects

(2020) Ya-Wen Cheng et al.   Cell Reports

Beneficial non-anticoagulant mechanisms underlying heparin treatment of COVID-19 patients

(2020) Baranca Buijsers et al.   EBioMedicine

Peptide and peptide-based inhibitors of SARS-CoV-2 entry

(2020) Desiree Schütz et al.   ADVANCED DRUG DELIVERY REVIEWS

Targeting ACE2 for COVID-19 Therapy: Opportunities and Challenges

(2020) Hongpeng Jia et al.   AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY

Protease targeted COVID-19 drug discovery and its challenges: Insight into viral main protease (Mpro) and papain-like protease (PLpro) inhibitors

(2020) Sk. Abdul Amin et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Baricitinib treatment resolves lower-airway macrophage inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques

(2020) Timothy N. Hoang et al.   CELL

Hypothesis: Alpha-1-antitrypsin is a promising treatment option for COVID-19

(2020) Xiyuan Bai et al.   MEDICAL HYPOTHESES

Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin

(2020) Courtney J. Mycroft-West et al.   THROMBOSIS AND HAEMOSTASIS

The SARS-CoV-2 Cytopathic Effect Is Blocked by Lysosome Alkalizing Small Molecules

(2020) Kirill Gorshkov et al.   ACS Infectious Diseases

Dispirotripiperazine-core compounds, their biological activity with a focus on broad antiviral property, and perspectives in drug design (mini-review)

(2020) Anna Egorova et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection

(2019) Naoko Iwata-Yoshikawa et al.   JOURNAL OF VIROLOGY

A family of PIKFYVE inhibitors with therapeutic potential against autophagy-dependent cancer cells disrupt multiple events in lysosome homeostasis

(2019) Gaurav Sharma et al.   Autophagy

Small molecule PIKfyve inhibitors as cancer therapeutics: Translational promises and limitations

(2019) Ognian C. Ikonomov et al.   TOXICOLOGY AND APPLIED PHARMACOLOGY

Discovery of novel nonpeptide small-molecule NRP1 antagonists: Virtual screening, molecular simulation and structural modification

(2019) Kewen Peng et al.   BIOORGANIC & MEDICINAL CHEMISTRY

ADAM proteases: Emerging role and targeting of the non-catalytic domains

(2019) Nayanendu Saha et al.   CANCER LETTERS

NRPa-308, a new neuropilin-1 antagonist, exerts in vitro anti-angiogenic and anti-proliferative effects and in vivo anti-cancer effects in a mouse xenograft model

(2018) Wang-Qing Liu et al.   CANCER LETTERS

Small Molecule Neuropilin-1 Antagonists Combine Antiangiogenic and Antitumor Activity with Immune Modulation through Reduction of Transforming Growth Factor Beta (TGFβ) Production in Regulatory T-Cells

(2018) Jonathan Powell et al.   JOURNAL OF MEDICINAL CHEMISTRY

NAADP-dependent Ca2+ signaling regulates Middle East respiratory syndrome-coronavirus pseudovirus translocation through the endolysosomal system

(2018) Gihan S. Gunaratne et al.   CELL CALCIUM

Carbohydrate-based peptidomimetics targeting neuropilin-1: Synthesis, molecular docking study and in vitro biological activities

(2016) Mylène Richard et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Inhibition of c-Rel DNA binding is critical for the anti-inflammatory effects of novel PIKfyve inhibitor

(2016) Masaomi Terajima et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Vacuolin-1 inhibits autophagy by impairing lysosomal maturation via PIKfyve inhibition

(2016) Osamu Sano et al.   FEBS LETTERS

Kinetic analysis and molecular modeling of the inhibition mechanism of roneparstat (SST0001) on human heparanase

(2016) Daniele Pala et al.   GLYCOBIOLOGY

Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)

(2016) Nan Zhou et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The structure of a furin-antibody complex explains non-competitive inhibition by steric exclusion of substrate conformers

(2016) Sven O. Dahms et al.   Scientific Reports

Protease inhibitors targeting coronavirus and filovirus entry

(2015) Yanchen Zhou et al.   ANTIVIRAL RESEARCH

Synthesis and Biological Evaluation of Indolyl-Pyridinyl-Propenones Having Either Methuosis or Microtubule Disruption Activity

(2015) Christopher J. Trabbic et al.   JOURNAL OF MEDICINAL CHEMISTRY

Circulating angiotensin-converting enzyme 2 activity in patients with chronic kidney disease without previous history of cardiovascular disease

(2015) Lidia Anguiano et al.   NEPHROLOGY DIALYSIS TRANSPLANTATION

Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment

(2015) Yasuteru Sakurai et al.   SCIENCE

Discovery of novel inhibitors of vascular endothelial growth factor-A–Neuropilin-1 interaction by structure-based virtual screening

(2014) Anna Starzec et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Structure–activity relationship study, target identification, and pharmacological characterization of a small molecular IL-12/23 inhibitor, APY0201

(2014) Nobuhiko Hayakawa et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Structure-based discovery of a small non-peptidic Neuropilins antagonist exerting in vitro and in vivo anti-tumor activity on breast cancer model

(2014) Lucia Borriello et al.   CANCER LETTERS

PIKfyve, a Class III PI Kinase, Is the Target of the Small Molecular IL-12/IL-23 Inhibitor Apilimod and a Player in Toll-like Receptor Signaling

(2013) Xinming Cai et al.   CHEMISTRY & BIOLOGY

Targeting VEGF signalling via the neuropilin co-receptor

(2012) Snezana Djordjevic et al.   DRUG DISCOVERY TODAY

Potent anti-respiratory syncytial virus activity of a cholestanol-sulfated tetrasaccharide conjugate

(2011) Anna Lundin et al.   ANTIVIRAL RESEARCH

Integration of Virtual and High Throughput Screening in Lead Discovery Settings

(2011) Timea Polgar et al.   COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING

Virtual High Throughput Screening in New Lead Identification

(2011) Preethi Badrinarayan et al.   COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING

Inhibition of SARS Pseudovirus Cell Entry by Lactoferrin Binding to Heparan Sulfate Proteoglycans

(2011) Jianshe Lang et al.   PLoS One

Sugar-based peptidomimetics as potential inhibitors of the vascular endothelium growth factor binding to neuropilin-1

(2010) Alexandre Novoa et al.   BIOORGANIC & MEDICINAL CHEMISTRY

In silico fragment-based drug design

(2010) Zenon D Konteatis   Expert Opinion on Drug Discovery

Small Molecule Inhibitors of the Neuropilin-1 Vascular Endothelial Growth Factor A (VEGF-A) Interaction

(2010) Ashley Jarvis et al.   JOURNAL OF MEDICINAL CHEMISTRY

A selective PIKfyve inhibitor blocks PtdIns(3,5)P2 production and disrupts endomembrane transport and retroviral budding

(2008) Harold B J Jefferies et al.   EMBO REPORTS

Assessment of Chemical Coverage of Kinome Space and Its Implications for Kinase Drug Discovery

(2008) Paul Bamborough et al.   JOURNAL OF MEDICINAL CHEMISTRY