An update review of emerging small-molecule therapeutic options for COVID-19

Autor: Dengke Tian, Liang Xin, Minge Wan, Xie Xiaolin, Zhang Dezhu, Wenqiang Cao, Liang Chengyuan, Liu Yuzhi, Li Han, Hong Liu, Xueqi Fu
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Coronaviruses
medicine.medical_treatment
viruses
Review
Pharmacology
chemistry.chemical_compound
0302 clinical medicine
nsps
Non-structural proteins

Chloroquine
Medicine
CoV
Coronavirus

CQ
Chloroquine

HA
Haemagglutinin

Molecular Targeted Therapy
Enzyme Inhibitors
DAAs
Direct-acting antiviral agents

biology
FDA
US Food and Drug Administration

Therapies
Investigational

HTAs
Host-targeting antivirals

MERS-CoV
Middle East respiratory syndrome coronavirus

General Medicine
Small molecule
PIP2
Phosphatidylinositol 4
5-bisphosphate

RMP
Ribavirin monophosphate

IFN
Interferon

N
Nucleocapsid protein

COVID-19
2019 Coronavirus disease

HIV
Human immunodeficiency virus

RBV
Ribavirin

NIAID
National Institute of Allergy and Infectious Diseases

030220 oncology & carcinogenesis
6MP
6-Mercaptopurine

BSAs
Broad-spectrum antiviral drugs

RDP
Ribavirin diphosphate

EBOV
Ebola virus

Transmembrane serine protease (TMPRSS2)
GTP
Guanosine triphosphate

medicine.drug
3CLpro
3C-Like protease

DHODH
Dihydroorotate dehydrogenase

6TG
6-Thioguanine

Papain-like protease (PLpro)
TGN
Trans-Golgi network

RM1-950
Favipiravir
TMPRSS2
HyCoSuL
Hybrid Combinatorial Substrate Library

Antiviral Agents
PP2A
Protein phosphatase 2A

SARS-CoV
Severe acute respiratory syndrome coronavirus

WHO
World Health Organization

CPE
Cytopathic effect

PLpro
Papain-like protease

03 medical and health sciences
EUA
Emergency use authorization

IRF3
Interferon regulatory factor 3

SAR
Structure-activity relationship

ACE2
Angiotensin-converting enzyme 2

S
Spike protein

SKP2
S-Phase kinase-associated protein 2

Humans
RdRp
RNA-dependent RNA polymerase

RTP
Ribavirin triphosphate

BECN1
Beclin1

ComputingMethodologies_COMPUTERGRAPHICS
Serine protease
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2

Protease
HC
QHydroxychloroquine

business.industry
SARS-CoV-2
Ribavirin
fungi
COVID-19
PC
Pro-protein convertase

DHO
Dihydroorotate

M
Membrane protein

RNA-dependent RNA polymerase (RdRp)
COVID-19 Drug Treatment
AMPK
AMP-activated protein kinase

CMK
Decanoyl-RVKR-chloromethylketone

Mpro
Main protease

030104 developmental biology
chemistry
3C-like protease (3CLpro)
E
Envelope protein

biology.protein
Dihydroorotate dehydrogenase
GM1
Monosialotetrahexosylganglioside 1

LPV/r
Lopinavir/ritonavir

Therapeutics. Pharmacology
ELs
Endolysosomes

business
IMPDH
Inosine monophosphate dehydrogenase
Zdroj: Biomedicine & Pharmacotherapy
Biomedicine & Pharmacotherapy, Vol 137, Iss, Pp 111313-(2021)
ISSN: 1950-6007
0753-3322
Popis: Graphical abstract
The SARS-CoV-2 outbreak and pandemic that began near the end of 2019 has posed a challenge to global health. At present, many candidate small-molecule therapeutics have been developed that can inhibit both the infection and replication of SARS-CoV-2 and even potentially relieve cytokine storms and other related complications. Meanwhile, host-targeted drugs that inhibit cellular transmembrane serine protease (TMPRSS2) can prevent SARS-CoV-2 from entering cells, and its combination with chloroquine and dihydroorotate dehydrogenase (DHODH) inhibitors can limit the spread of SARS-CoV-2 and reduce the morbidity and mortality of patients with COVID-19. The present article provides an overview of these small-molecule therapeutics based on insights from medicinal chemistry research and focuses on RNA-dependent RNA polymerase (RdRp) inhibitors, such as the nucleoside analogues remdesivir, favipiravir and ribavirin. This review also covers inhibitors of 3C-like protease (3CLpro), papain-like protease (PLpro) and other potentially innovative active ingredient molecules, describing their potential targets, activities, clinical status and side effects.
Databáze: OpenAIRE