Abstract The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many small molecules with potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition of viral proteins such as RdRp and M pro , interference of host enzymes including ACE2 and proteases, and blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, and NLRP3 pathways, are regarded feasible in drug development. The development of small molecules to treat COVID-19 has been achieved by several strategies, including computer-aided lead compound design and screening, natural product discovery, drug repurposing, and combination therapy. Several small molecules representative by remdesivir and paxlovid have been proved or authorized emergency use in many countries. And many candidates have entered clinical-trial stage. Nevertheless, due to the epidemiological features and variability issues of SARS-CoV-2, it is necessary to continue exploring novel strategies against COVID-19. This review discusses the current findings in the development of small molecules for COVID-19 treatment. Moreover, their detailed mechanism of action, chemical structures, and preclinical and clinical efficacies are discussed. 

/pdf/small-molecules-in-the-treatment-of-covid-19-313d7e1y.pdf

Small molecules in the treatment of COVID-19

Abstract Background Natural products can serve as one of the alternatives, exhibiting high potential for the treatment and prevention of COVID-19, caused by SARS-CoV-2. Herein, we report a screening platform to test the antiviral efficacy of a natural product library against SARS-CoV-2 and verify their activity using lung organoids. Methods Since SARS-CoV-2 is classified as a risk group 3 pathogen, the drug screening assay must be performed in a biosafety level 3 (BSL-3) laboratory. To circumvent this limitation, pseudotyped viruses (PVs) have been developed as replacements for the live SARS-CoV-2. We developed PVs containing spikes from Delta and Omicron variants of SARS-CoV-2 and improved the infection in an angiotensin-converting enzyme 2 (ACE2)-dependent manner. Human induced pluripotent stem cells (hiPSCs) derived lung organoids were generated to test the SARS-CoV-2 therapeutic efficacy of natural products. Results Flavonoids from our natural product library had strong antiviral activity against the Delta- or Omicron-spike-containing PVs without affecting cell viability. We aimed to develop strategies to discover the dual function of either inhibiting infection at the beginning of the infection cycle or reducing spike stability following SARS-CoV-2 infection. When lung cells are already infected with the virus, the active flavonoids induced the degradation of the spike protein and exerted anti-inflammatory effects. Further experiments confirmed that the active flavonoids had strong antiviral activity in lung organoid models. Conclusion This screening platform will open new paths by providing a promising standard system for discovering novel drug leads against SARS-CoV-2 and help develop promising candidates for clinical investigation as potential therapeutics for COVID-19. Graphical Abstract 

/pdf/development-of-a-screening-platform-to-discover-natural-2qxn6zc0.pdf

Development of a screening platform to discover natural products active against SARS-CoV-2 infection using lung organoid models

Abstract The coronavirus disease 2019 (COVID‐19) pandemic has affected a large portion of the global population, both physically and mentally. Current evidence suggests that the rapidly evolving coronavirus subvariants risk rendering vaccines and antibodies ineffective due to their potential to evade existing immunity, with enhanced transmission activity and higher reinfection rates that could lead to new outbreaks across the globe. The goal of viral management is to disrupt the viral life cycle as well as to relieve severe symptoms such as lung damage, cytokine storm, and organ failure. In the fight against viruses, the combination of viral genome sequencing, elucidation of the structure of viral proteins, and identifying proteins that are highly conserved across multiple coronaviruses has revealed many potential molecular targets. In addition, the time‐ and cost‐effective repurposing of preexisting antiviral drugs or approved/clinical drugs for these targets offers considerable clinical advantages for COVID‐19 patients. This review provides a comprehensive overview of various identified pathogenic targets and pathways as well as corresponding repurposed approved/clinical drugs and their potential against COVID‐19. These findings provide new insight into the discovery of novel therapeutic strategies that could be applied to the control of disease symptoms emanating from evolving SARS‐CoV‐2 variants.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/mco2.254

Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS‐CoV‐2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the coronavirus disease 2019 (COVID-19) pandemic with more than 6 million deaths worldwide. Flavonoids from the genus Erythrina may inhibit SARS-CoV-2, targeting 3C-like protease (3CL pro ), an enzyme essential in the virus’s growth. Hence, this study aimed to screen 378 flavonoids from Erythrina against 3CL pro , using molecular docking, Lipinski’s rule of five, and in silico absorption, distribution, metabolism, excretion, and toxicity. These virtual screening campaigns suggest that 108 flavonoids have stronger binding energy values (−13.23 to −10.20 kcal/mol) than the N3 inhibitor (−10.14 kcal/mol) as the reference ligand. Some 33 of these flavonoids may be hepatoxicity- and mutagenicity-free. They are also non-hERG I and II inhibitors. Two of them, orientanol E ( 171 ) and erycaffra F ( 57 ), have binding energy values in the top 10 hits and good absorption profiles, despite their poor distribution properties. They may have a high bioavailability in the body and be excreted from the body through feces. Conducted molecular dynamics simulations also support orientanol E ( 171 ) and erycaffra F ( 57 ) as 3CL pro inhibitor candidates. Our study suggests that flavonoids from Erythrina have potential as 3CL pro inhibitors, which help guide further in vitro and in vivo experiments in COVID-19 drug development.

/pdf/virtual-screening-campaigns-and-admet-evaluation-to-unlock-61rwd3t0.pdf

Virtual screening campaigns and ADMET evaluation to unlock the potency of flavonoids from Erythrina as 3CLpro SARS-COV-2 inhibitors

Since the identification of COVID-19 in China in December 2019, scientists and researchers have been continuously discovering and proposing drugs for this disease. Many efforts have been made to examine medicinal plants known for their benefits in treating infectious diseases and for their actions in boosting of the immune system. Repurposing of FDA-approved antiviral drugs has also been advanced. However, no effective antiviral drug specific to COVID-19 is currently available. To contribute in the search for drugs against this disease, the present study aims to identify secondary metabolites (or phytomolecules) possessing an inhibitory effect on the replication of SARS-CoV-2, the etiological agent of COVID-19. 76 secondary metabolites from 16 aromatics medicinal plants from Madagascar were uploaded to the PubChem server. Then, they were docked with 5 non-structural proteins (nsps) of SARS-CoV-2, including the main protease, the papain-type protease, the RNA-dependent RNA polymerase, the helicase and the 2'-O-methyltransferase, using the Autodock Vina program integrated in the PYRIX 0.8 software. The results show that 5 secondary metabolites of Cinnamosma fragrans (Capsicodendrin, Ugandensolide, Cinnamolide, Tocotrienol and Pereniporin B) have good affinity with the 5 nsps of SARS-CoV-2 and can inhibit its functions in viral replication. Therefore, these phytomolecules could be used in the development of antiviral drugs against SARS-CoV-2 and COVID-19. Nevertheless, further in vitro and in vivo studies should be performed to valorize these results obtained by the in silico method.

/pdf/molecular-docking-study-of-seventy-six-phytomolecules-from-24wjlpbk.pdf

Molecular docking study of seventy-six phytomolecules from sixteen aromatics medicinal plants as promising inhibitors of five non-structural proteins of SARS-CoV-2

Abstract Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently poses a threat to human health. 3C-like proteinase (3CLpro) plays an important role in the viral life cycle. Hence, it is considered an attractive antiviral target protein. Whole-genome sequencing showed that the sequence homology between SARS-CoV-2 3CLpro and SARS-CoV 3CLpro is 96.08%, with high similarity in the substrate-binding region. Thus, assessing peptidomimetic inhibitors of SARS-CoV 3CLpro could accelerate the development of peptidomimetic inhibitors for SARS-CoV-2 3CLpro. Accordingly, we herein discuss progress on SARS-CoV-2 3CLpro peptidomimetic inhibitors. Inflammation plays a major role in the pathophysiological process of COVID-19. Small-molecule compounds targeting 3CLpro with both antiviral and anti-inflammatory effects are also briefly discussed in this paper.

Progress on SARS-CoV-2 3CLpro Inhibitors: Inspiration from SARS-CoV 3CLpro Peptidomimetics and Small-Molecule Anti-Inflammatory Compounds

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Qinghong Lin

Author Tools

Chat about Author

Papers

Progress on SARS-CoV-2 3CLpro Inhibitors: Inspiration from SARS-CoV 3CLpro Peptidomimetics and Small-Molecule Anti-Inflammatory Compounds