New Scientist
Volume 245, Issue 3275, 28 March 2020, Pages 10-11
It is easy to spread the virus without realising you are ill, reports Graham Lawton
WITH more than 380,000 confirmed cases worldwide, one thing is clear about the new coronavirus: it is very good at infecting people. Now studies are starting to reveal just how infectious it is – and when a person with covid-19 is most likely to spread the virus.
Epidemiology
New Scientist
Volume 245, Issue 3275, March 2020, Pages 44-48
There has never been a more important time to keep your immune system fit and healthy. And as Graham Lawton discovers, there are now ways to keep it younger than you are.
WASH your hands religiously for 20 seconds, sneeze into your elbow, avoid touching your face, stay 1 meter away from all other people and, as a last resort, self-quarantine for a week with only your emergency rations for company. If you want to avoid getting the new coronavirus, all of these are a good idea. But ultimately, one of the most important things standing between you and a deadly bout of COVID-19 is your immune system.
Epidemiology
Antiviral Research
Volume 85, Issue 3, March 2010, Pages 551-555
Because outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV) might reemerge, identifying antiviral compounds is of key importance. Previously, we showed that the cellular factor TNF-α converting enzyme (TACE), activated by the spike protein of SARS-CoV (SARS-S protein), was positively involved in viral entry, implying that TACE is a possible target for developing antiviral compounds. To demonstrate this possibility, we here tested the effects of TACE inhibitors on viral entry. In vitro and in vivo data revealed that the TACE inhibitor TAPI-2 attenuated entry of both pseudotyped virus expressing the SARS-S protein in a lentiviral vector backbone and infectious SARS-CoV. TAPI-2 blocked both the SARS-S protein-induced shedding of angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV, and TNF-α production in lung tissues. Since the downregulation of ACE2 by SARS-S protein was proposed as an etiological event in the severe clinical manifestations, our data suggest that TACE antagonists block SARS-CoV infection and also attenuate its severe clinical outcome.
SARS-CoV, TACE, ACE2, Shedding
Bioorganic & Medicinal Chemistry Letters
Volume 20, Issue 6, 15 March 2010, Pages 1873-1876
Quinone-methide triterpenes, celastrol (1), pristimerin (2), tingenone (3), and iguesterin (4) were isolated from Triterygium regelii and dihydrocelastrol (5) was synthesized by hydrogenation under palladium catalyst. Isolated quinone-methide triterpenes (1–4) and 5 were evaluated for SARS-CoV 3CLpro inhibitory activities and showed potent inhibitory activities with IC50 values of 10.3, 5.5, 9.9, and 2.6 μM, respectively, whereas the corresponding 5 having phenol moiety was observed in low activity (IC50 = 21.7 μM). As a result, quinone-methide moiety in A-ring and more hydrophobic E-ring assist to exhibit potent activity. Also, all quinone-methide triterpenes 1–4 have proven to be competitive by the kinetic analysis.
SARS-CoV, 3CLpro, Tripterygium regelii, Quinone-methide, Celastrol, Iguesterin
Bioorganic & Medicinal Chemistry
Volume 18, Issue 22, 15 November 2010, Pages 7940-7947
As part of our search for botanical sources of SARS-CoV 3CLpro inhibitors, we selected Torreya nucifera, which is traditionally used as a medicinal plant in Asia. The ethanol extract of T. nucifera leaves exhibited good SARS-CoV 3CLpro inhibitory activity (62% at 100 μg/mL). Following bioactivity-guided fractionation, eight diterpenoids (1–8) and four biflavonoids (9–12) were isolated and evaluated for SARS-CoV 3CLpro inhibition using fluorescence resonance energy transfer analysis. Of these compounds, the biflavone amentoflavone (9) (IC50 = 8.3 μM) showed most potent 3CLpro inhibitory effect. Three additional authentic flavones (apigenin, luteolin and quercetin) were tested to establish the basic structure–activity relationship of biflavones. Apigenin, luteolin, and quercetin inhibited 3CLpro activity with IC50 values of 280.8, 20.2, and 23.8 μM, respectively. Values of binding energy obtained in a molecular docking study supported the results of enzymatic assays. More potent activity appeared to be associated with the presence of an apigenin moiety at position C-3′ of flavones, as biflavone had an effect on 3CLpro inhibitory activity.
SARS-CoV 3CLpro,Torreya nucifera, Biflavonoid, Amentoflavone
Virology
Volume 405, Issue 1, 15 September 2010, Pages 139-148
Coronaviruses are enveloped RNA viruses that generally cause mild disease in humans. However, the recently emerged coronavirus that caused severe acute respiratory syndrome (SARS-CoV) is the most pathogenic human coronavirus discovered to date. The SARS-CoV spike (S) protein mediates virus entry by binding cellular receptors and inducing fusion between the viral envelope and the host cell membrane. Coronavirus S proteins are palmitoylated, which may affect function. Here, we created a non-palmitoylated SARS-CoV S protein by mutating all nine cytoplasmic cysteine residues. Palmitoylation of SARS-CoV S was required for partitioning into detergent-resistant membranes and for cell–cell fusion. Surprisingly, however, palmitoylation of S was not required for interaction with SARS-CoV M protein. This contrasts with the requirement for palmitoylation of mouse hepatitis virus S protein for interaction with M protein and may point to important differences in assembly and infectivity of these two coronaviruses.
coronavirus, SARS-CoV, spike, palmitoylation, fusion, detergent-resistant membranes, trafficking
Bioorganic & Medicinal Chemistry Letters
Volume 20, Issue 12, 15 June 2010, Pages 3569-3572
A series of 2-(benzylthio)-6-oxo-4-phenyl-1,6-dihydropyrimidine as SARS-CoV 3CL protease inhibitors were developed and their potency was evaluated by in vitro protease inhibitory assays. Two candidates had encouraging results for the development of new anti-SARS compounds.
SARS-CoV, Pyrimidines
Bioorganic & Medicinal Chemistry Letters
Volume 20, Issue 12, 15 June 2010, Pages 3569-3572
A series of 2-(benzylthio)-6-oxo-4-phenyl-1,6-dihydropyrimidine as SARS-CoV 3CL protease inhibitors were developed and their potency was evaluated by in vitro protease inhibitory assays. Two candidates had encouraging results for the development of new anti-SARS compounds.
SARS-CoV, Pyrimidines
Antiviral Research
Volume 85, Issue 3, March 2010, Pages 551-555
Because outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV) might reemerge, identifying antiviral compounds is of key importance. Previously, we showed that the cellular factor TNF-α converting enzyme (TACE), activated by the spike protein of SARS-CoV (SARS-S protein), was positively involved in viral entry, implying that TACE is a possible target for developing antiviral compounds. To demonstrate this possibility, we here tested the effects of TACE inhibitors on viral entry. In vitro and in vivo data revealed that the TACE inhibitor TAPI-2 attenuated entry of both pseudotyped virus expressing the SARS-S protein in a lentiviral vector backbone and infectious SARS-CoV. TAPI-2 blocked both the SARS-S protein-induced shedding of angiotensin-converting enzyme 2 (ACE2), a receptor of SARS-CoV, and TNF-α production in lung tissues. Since the downregulation of ACE2 by SARS-S protein was proposed as an etiological event in the severe clinical manifestations, our data suggest that TACE antagonists block SARS-CoV infection and also attenuate its severe clinical outcome.
SARS-CoV, TACE, ACE2, Shedding
Bioorganic & Medicinal Chemistry Letters
Volume 20, Issue 6, 15 March 2010, Pages 1873-1876
Young Bae Ryu, Su-Jin Park, Young Min Kim, Ju-YeonLee, Woo Duck Seo, Jong SunChang, Ki Hun Park, Mun-Chual Rho, Woo Song Lee
Quinone-methide triterpenes, celastrol (1), pristimerin (2), tingenone (3), and iguesterin (4) were isolated from Triterygium regelii and dihydrocelastrol (5) was synthesized by hydrogenation under palladium catalyst. Isolated quinone-methide triterpenes (1–4) and 5 were evaluated for SARS-CoV 3CLpro inhibitory activities and showed potent inhibitory activities with IC50 values of 10.3, 5.5, 9.9, and 2.6 μM, respectively, whereas the corresponding 5 having phenol moiety was observed in low activity (IC50 = 21.7 μM). As a result, quinone-methide moiety in A-ring and more hydrophobic E-ring assist to exhibit potent activity. Also, all quinone-methide triterpenes 1–4 have proven to be competitive by the kinetic analysis.
SARS-CoV, 3CLpro, Tripterygium regelii, Quinone-methide, Celastrol, Iguesterin