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Discovery of New Fusion Inhibitor Peptides against SARS-CoV-2 by Targeting the Spike S2 Subunit
( Mahmoud Kandeel ),( Mizuki Yamamoto ),( Hideki Tani ),( Ayako Kobayashi ),( Jin Gohda ),( Yasushi Kawaguchi ),( Byoung Kwon Park ),( Hyung-joo Kwon ),( Jun-ichiro Inoue ),( Abdallah Alkattan ) 한국응용약물학회 2021 Biomolecules & Therapeutics(구 응용약물학회지) Vol.29 No.3
A novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), caused a worldwide pandemic. Our aim in this study is to produce new fusion inhibitors against SARS-CoV-2, which can be the basis for developing new antiviral drugs. The fusion core comprising the heptad repeat domains (HR1 and HR2) of SARS-CoV-2 spike (S) were used to design the peptides. A total of twelve peptides were generated, comprising a short or truncated 24-mer (peptide #1), a long 36-mer peptide (peptide #2), and ten peptide #2 analogs. In contrast to SARS-CoV, SARS-CoV-2 S-mediated cell-cell fusion cannot be inhibited with a minimal length, 24-mer peptide. Peptide #2 demonstrated potent inhibition of SARS-CoV-2 S-mediated cell-cell fusion at 1 μM concentration. Three peptide #2 analogs showed IC50 values in the low micromolar range (4.7-9.8 μM). Peptide #2 inhibited the SARSCoV- 2 pseudovirus assay at IC50=1.49 μM. Given their potent inhibition of viral activity and safety and lack of cytotoxicity, these peptides provide an attractive avenue for the development of new prophylactic and therapeutic agents against SARS-CoV-2.
Biological activity of an Indian medical plant, Indigofera cordifolia
Rao, Bhattiprolu Kesava,Kawase, Masami,Tanaka, Toru,Tani, Satoru,Motohashi, Noboru,Satoh, Kazue,Sakagami, Hiroshi,Terakubo, Shigemi,Nakashima, Hideki,Wolfard, Krisztina,Molnar, Joseph Kyung Hee Oriental Medicine Research Center 2004 Oriental pharmacy and experimental medicine Vol.4 No.3
The ethanol extract of Indigofera cordifolia was studied for in vivo gastroprotective activity, cytotoxic activity against oral tumor and normal cells, multidrug resistance (MDR) reversal activity, anti-human immunodeficiency virus (HIV) activity and radical scavenging activity. The extract of I. cordifolia showed potent gastric mucosal protective activity against stomach injury induced by HCl/EtOH solution. However, the gastroprotective activity could not be related to the radical mechanism, because the extract weakly scavenged both OH radical and $O_2*^-$. The extract also showed promising levels of MDR-reversing activity. This study demonstrates the tumor-specific cytotoxic action of the plant extract. However, the extract had no anti-HIV activity. From above results, the study suggests the medicinal importance of I. cordiforia extract.