Novel inhibitors of severe acute respiratory syndrome coronavirus entry that act by three distinct mechanisms.

Journal of Virology
Adeyemi O AdedejiStefan G Sarafianos

Abstract

Severe acute respiratory syndrome (SARS) is an infectious and highly contagious disease that is caused by SARS coronavirus (SARS-CoV) and for which there are currently no approved treatments. We report the discovery and characterization of small-molecule inhibitors of SARS-CoV replication that block viral entry by three different mechanisms. The compounds were discovered by screening a chemical library of compounds for blocking of entry of HIV-1 pseudotyped with SARS-CoV surface glycoprotein S (SARS-S) but not that of HIV-1 pseudotyped with vesicular stomatitis virus surface glycoprotein G (VSV-G). Studies on their mechanisms of action revealed that the compounds act by three distinct mechanisms: (i) SSAA09E2 {N-[[4-(4-methylpiperazin-1-yl)phenyl]methyl]-1,2-oxazole-5-carboxamide} acts through a novel mechanism of action, by blocking early interactions of SARS-S with the receptor for SARS-CoV, angiotensin converting enzyme 2 (ACE2); (ii) SSAA09E1 {[(Z)-1-thiophen-2-ylethylideneamino]thiourea} acts later, by blocking cathepsin L, a host protease required for processing of SARS-S during viral entry; and (iii) SSAA09E3 [N-(9,10-dioxo-9,10-dihydroanthracen-2-yl)benzamide] also acts later and does not affect interactions of SARS-S w...Continue Reading

References

Jun 6, 2000·Journal of Biomolecular Screening·J H ZhangK R Oldenburg
Jun 22, 2000·Biochemical and Biophysical Research Communications·J K HarttP M Murphy
Aug 31, 2000·Annual Review of Biochemistry·J J Skehel, D C Wiley
Feb 27, 2001·Journal of Virology·J T MangorG W Blissard
Jul 14, 2001·Chemistry & Biology·V RazinkovG Krishnamurthy
Apr 3, 2003·The New England Journal of Medicine·Susan M PoutanenUNKNOWN Canadian Severe Acute Respiratory Syndrome Study Team
May 8, 2003·JAMA : the Journal of the American Medical Association·Christopher M BoothAllan S Detsky
Jun 5, 2003·Lancet·John M NichollsJ S Malik Peiris
Oct 3, 2003·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Sandra R KnowlesLarissa Matukas
Dec 4, 2003·Biochemical and Biophysical Research Communications·Xiaodong XiaoDimiter S Dimitrov
Dec 13, 2003·The Journal of Biological Chemistry·Swee Kee WongMichael Farzan
Dec 17, 2003·Cell·Dimiter S Dimitrov
Jan 23, 2004·Nature·Theodore S Jardetzky, Robert A Lamb
Mar 5, 2004·The Journal of Biological Chemistry·Brian TripetRobert S Hodges
Mar 11, 2004·Proceedings of the National Academy of Sciences of the United States of America·Graham SimmonsPaul Bates
May 26, 2004·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Michael D Miller, Daria J Hazuda
Mar 26, 2005·The EMBO Journal·Wenhui LiMichael Farzan
Jul 5, 2005·Virology·Tonie CilliersLynn Morris
Aug 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Graham SimmonsPaul Bates
Dec 13, 2005·The Journal of Biological Chemistry·I-Chueh HuangHyeryun Choe
Jan 3, 2006·Advances in Virus Research·Keith Bupp, Monica J Roth
Jun 6, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Rodger D MacArthur, Richard M Novak
Aug 12, 2008·Clinical Therapeutics·Sharon S Lieberman-BlumJuan C Bandres
Oct 22, 2008·The Journal of General Virology·Hua WangRollie J Clem
Feb 6, 2009·Drugs·Birgitt Dau, Mark Holodniy
May 12, 2009·Nature Reviews. Microbiology·Stanley Perlman, Jason Netland

❮ Previous
Next ❯

Citations

Oct 23, 2013·Current Infectious Disease Reports·Dana HawkinsonLara Danziger-Isakov
Nov 23, 2013·Future Medicinal Chemistry·Adeyemi O Adedeji, Stefan G Sarafianos
Jul 6, 2014·Current Opinion in Virology·Adeyemi O Adedeji, Stefan G Sarafianos
Sep 10, 2013·Antiviral Research·Rolf Hilgenfeld, Malik Peiris
Nov 13, 2013·Nature Reviews. Microbiology·Rachel L GrahamRalph S Baric
Apr 26, 2020·British Journal of Pharmacology·Krishna Sriram, Paul A Insel
Jul 24, 2020·Journal of Biomolecular Structure & Dynamics·Preeti PandeyShashikant Ray
Aug 28, 2020·Medicinal Research Reviews·Thanigaimalai PillaiyarMaheswaran Easwaran
May 22, 2020·Journal of Translational Internal Medicine·Mengyuan LiuJianping Li
Jun 26, 2020·Clinical Microbiology Reviews·Kuldeep DhamaAlfonso J Rodriguez-Morales
Jul 10, 2020·Journal of Drug Targeting·Jyoti VermaMaitreyi S Rajala
Oct 2, 2020·Pharmaceuticals·Anastasiia I Petushkova, Andrey A Zamyatnin
Jan 9, 2019·Frontiers in Microbiology·Diego R HijanoRandall T Hayden
May 10, 2020·Cellular and Molecular Neurobiology·Juan M Saavedra
Jun 21, 2020·Journal of Clinical Medicine·David WuDeepak Shukla
Sep 16, 2020·Journal of Biomolecular Structure & Dynamics·Abhinav ChoubeyProsenjit Mondal
Jul 28, 2020·International Journal of Molecular Sciences·Alessandra FierabracciPaolo Rossi
Aug 28, 2020·Frontiers in Pharmacology·Bachir Benarba, Atanasio Pandiella
Mar 24, 2020·Indian Journal of Pharmacology·Manisha PrajapatBikash Medhi
Sep 10, 2020·Frontiers in Microbiology·Igor de Andrade SantosAna Carolina Gomes Jardim
Aug 28, 2020·Frontiers in Cardiovascular Medicine·Annamaria MascoloAnnalisa Capuano
Oct 9, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Raphael E F de PaivaFernando R G Bergamini
Oct 20, 2020·Frontiers in Immunology·Narasimha M BeerakaGjumrakch Aliev
Dec 19, 2020·Frontiers in Microbiology·Tanveer AhmadSyed Mansoor Ali
Aug 26, 2020·European Journal of Pharmacology·Nousheen BibiMohammad Amjad Kamal
Jan 12, 2021·Expert Review of Clinical Pharmacology·Chiranjib ChakrabortyGovindasamy Agoramoorthy
Jan 14, 2021·Journal of Biomedical Science·Ioannis P TrougakosMeletios A Dimopoulos
Jan 19, 2021·Briefings in Bioinformatics·Yanqing YangWeiliang Zhu

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Hereditary Sensory Autonomic Neuropathy

Hereditary Sensory Autonomic Neuropathies are a group of inherited neurodegenerative disorders characterized clinically by loss of sensation and autonomic dysfunction. Here is the latest research on these neuropathies.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Landau-Kleffner Syndrome

Landau Kleffner syndrome (LKS), also called infantile acquired aphasia, acquired epileptic aphasia, or aphasia with convulsive disorder, is a rare childhood neurological syndrome characterized by the sudden or gradual development of aphasia (the inability to understand or express language) and an abnormal electroencephalogram. Discover the latest research on LKS here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.