トピックス New Scientific Outputs related to COVID-19

トピックス

5. Report on Rapid and accurate detection of novel coronavirus SARS-CoV-2 using CRISPR-Cas3

Title: Rapid and accurate detection of novel coronavirus SARS-CoV-2 using CRISPR-Cas3
Preprint server: MedRxivPosted Date: 2020/6/2
URL: https://www.medrxiv.org/content/10.1101/2020.06.02.20119875v1
Authors:
Kazuto Yoshimi, Kohei Takeshita, Seiya Yamayoshi, Satomi Shibumura, Yuko Yamauchi, Masaki Yamamoto, Hiroshi Yotsuyanagi, Yoshihiro Kawaoka, Tomoji Mashimo

Outline:
New method (CONAN method) to detect viral RNA easily and accurately using domestic genome editing technology CRISPR-Cas3 has been developed. This new CRISPR test has a high detection sensitivity that is almost the same as that of PCR test, and it can be tested within 40 minutes without using precision equipment like the antigen test method, so it can be used at various places such as medical sites. It will be possible to perform COVID-19 diagnosis quickly, cheaply and reliably.

概要:
国産ゲノム編集技術CRISPR-Cas3によりサンプル中の微量なウイルスRNAを正確に検出する手法(CONAN法)を開発した。SARS-CoV-2のウイルスRNAを用いて検査を行った結果、数十個程度のサンプルでも、最短40分以内に試験紙で検出することに成功した。この新しいCRISPR検査法は、PCR検査法とほぼ同等の高い検出感度を持ち、抗原検査法のように精密な機器を使わずに検査できるため、医療現場などの様々な場所で「素早く、安く、確実に」COVID-19診断を行うことが可能になる。
 

(Last updated: 2020/06/05)

4. Report on SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is further increased by a naturally occurring elongation variant

Title: SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is further increased by a naturally occurring elongation variant
Preprint server: BioRxivPosted Date: 2020/5/11
URL: https://doi.org/10.1101/2020.05.11.088179
Authors:
Yoriyuki Konno, Izumi Kimura, Keiya Uriu, Masaya Fukushi, Takashi Irie, Yoshio Koyanagi, So Nakagawa, Kei Sato

Outline:
ORF3b of SARS-CoV-2 and related bat and pangolin viruses is a potent IFN antagonist. SARS-CoV-2 ORF3b suppresses IFN induction more efficiently than SARS-CoV ortholog. The anti-IFN activity of ORF3b depends on the length of its C-terminus. An ORF3b with increased IFN antagonism was isolated from two severe COVID-19 cases.

概要:
最近、新型コロナウイルス感染者の病態とインターフェロン応答の弱さが関係することが報告されている。われわれは、新型コロナウイルスのORF3b遺伝子が強いインターフェロン抑制効果を持つこと、ORF3bの変異によって、より病原性の高いウイルスが出現する可能性があることを示した。

(Last updated: 2020/06/05)

3. Report on docking model and pharmacological activity of Nelfinavir

Title: Multidrug treatment with nelfinavir and cepharanthine against COVID-19
Preprint server: BioRxivPosted Date: 2020/4/14
DOI: https://doi.org/10.1101/2020.04.14.039925
Authors:
Hirofumi Ohashi, Koichi Watashi, Wakana Saso, Kaho Shionoya, Shoya Iwanami, Takatsugu Hirokawa, Tsuyoshi Shirai, Shigehiko Kanaya, Yusuke Ito, Kwang Su Kim, Kazane Nishioka, Shuji Ando, Keisuke Ejima, Yoshiki Koizumi, Tomohiro Tanaka, Shin Aoki, Kouji Kuramochi, Tadaki Suzuki, Katsumi Maenaka, Tetsuro Matano, Masamichi Muramatsu, Masayuki Saijo, Kazuyuki Aihara, Shingo Iwami, Makoto Takeda, Jane A. McKeating, Takaji Wakita
Outline:
Mathematical modeling in vitro antiviral activity coupled with the known pharmacokinetics for these drugs predicts that Nelfinavir will facilitate viral clearance. Combining Nelfinavir/Cepharanthine enhanced their predicted efficacy to control viral proliferation, to ameliorate both the progression of disease and risk of transmission. In summary, this study identifies a new multidrug combination treatment for COVID-19.

概要:

  • バーチャルスクリーニングでヒットした化合物のうち、ネルフィナビルについて感染研にて抗ウイルス活性を評価したところ有効性が見いだされた。
  • 感染研が見いだしたセファランチンについて、ドッキングモデルを作製。
  • 両者の併用のメリットについて議論。
(Last updated: 2020/06/05)

2. Report on Knowledge-based structural models of SARS-CoV-2 proteins and their complex with potential drugs

Title: Knowledge-based structural models of SARS-CoV-2 proteins and their complex with potential drugs
Preprint server: ChemRxivPosted Date: 2020/03/24
URL: https://chemrxiv.org/articles/Knowledge-Based_Structural_Models_of_SARS-CoV-2_Proteins_and_Their_Complex_with_Potential_Drugs/12021330
Authors:
Atsushi Hijikata, Clara Shionyu-Mitsuyama, Setsu Nakae, Masafumi Shionyu, Motonori Ota, Shigehiko Kanaya, Tsuyoshi Shirai
Outline:
The World Health Organization (WHO) has declared a pandemic of the 2019 novel coronavirus SARS-CoV-2 infection (COVID-19). There is, however, no confirmed anti-COVID-19 therapeutic currently. In order to assist structure-based discovery of repurposing drugs against this disease, knowledge-based models of SARS-CoV-2 proteins were constructed, and the ligand molecules in the template structures were compared with approved/experimental drugs and components of natural medicines. The models suggested several drugs, such as carfilzomib, sinefungin, tecadenoson, and trabodenoson, as potential drugs for COVID-19.
(Last updated: 2020/06/05)

1. Report on key interactions between SARS-CoV-2 main protease and inhibitor drug candidates

Title: Identification of Key Interactions Between SARS-CoV-2 Main Protease and Inhibitor Drug Candidates
Preprint server: ChemRxivPosted Date: 2020/03/23
URL: https://chemrxiv.org/articles/Identification_of_Key_Interactions_Between_SARS-CoV-2_Main_Protease_and_Inhibitor_Drug_Candidates/12009636
Authors:
Ryunosuke Yoshino, Nobuaki Yasuo, Masakazu Sekijima
Outline:
We revealed key interactions between SARS-CoV-2 Mpro and three drug candidates by performing pharmacophore modeling and 1μs molecular dynamics (MD) simulations.

概要:

  • SARS-CoV-2のメインプロテアーゼと既存のプロテアーゼ阻害薬の重要な相互作用を、ファーマコフォアモデリングとMDシミュレーションにより明らかにした。
(Last updated: 2020/06/05)

最終更新日 令和2年6月24日