塩野義口服感冒剂 S-033188

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Preetika Rana, Drug Maker: Pill Kill Flu in a Day; Japan's Shionogi to apply for US approval this summer for experimental treatment. Wall Street Journal, Feb 12, 2018.
https://www.wsj.com/articles/exp ... in-a-day-1518264004
https://www.dailywire.com/news/2 ... -single-joseph-curl

Quote:

"A late-stage trial [phase III of a clinical trial] on Japanese and American flu patients found that for the people who took the Shionogi & Co  compound, the median time taken to wipe out the virus was 24 hours. That is much quicker than any other flu drug on the market, including Roche AG's Tamiflu, which the trial [one needs to show a new drug is better than existing drugs] showed took three times longer to achieve the same result.

"Also, Shionogi's experimental drug requires only a single dose, while patients need to take two doses of Tamiflu a day, for five days.

"Scientists at the Japanese company leveraged their work on a blockbuster anti-HIV drug to create the compound, which works differently from existing flu medicines. It blocks the flu virus from hijacking human cellular machinery, Chief Executive Isao Teshirogi said. Switzerland’s Roche has acquired the international license to distribute Shionogi's experimental drug.

Note:
(a) There is no need to read the rest.
(b) Take notice that flu victims starts infecting others through sneezing before that victim develops symptoms.

(c) Shionogi & Company, Limited  塩野義製薬株式会社 (founded by Saburō SHIONOGI 塩野義 三郎 in 1878 in Osaka, which remains its headquarters; its logo signifies a single 分銅 for 天秤)
(i) The kanji 塩 has "en" and "shio" as its Chinese and Japanese pronunciations, respectively.
(ii) For the logo, see the left upper corner of the home page:
http://www.shionogi.co.jp/en/
(iii) 分銅
https://ja.wikipedia.org/wiki/分銅
(section 4 江戸時代の後藤分銅: photo)

(d) How an influenza virus enters and eventually departs from the host cell.
(i) The surface of an influenza virus (for humans and birds alike) contains two proteins: hemagglutinin and neuraminidase.
(A) hemagglutinin (influenza)
https://en.wikipedia.org/wiki/Hemagglutinin_(influenza)
binds to "sialic acid" (derivatives of neuraminic acid; etymology: from Greek noun sialo for saliva) IN glycoproteins of cell membranes. By this, an influenza virus was swallowed into the cell, like a Trojan horse.
(B) viral neuraminidase
https://en.wikipedia.org/wiki/Viral_neuraminidase
(section 1 Function)
(ii) An influenza virus for humans contains 7 or 8 pieces of single-stranded RNA (all negative-sense).
(iii) In humans, genetic information is coded in DNA (both inside the nucleus 细胞核 and mitochondria 粒线体). In both places, DNA is transcribed into RNA, which is in turn translated into proteins (I am talking about only mRNA -- m for messenger -- not transfer RNA or ribosomal RNA).
(iv) A (linear) mRNA has a 5' (pronounced "five prime") end and a 3' end. The 5' end is "capped 戴帽子." See five-prime cap
https://en.wikipedia.org/wiki/Five-prime_cap
(the first figure)
(v) After a influenza virus enters a human cell, it must do "cap snatching" -- nabbing several mRNAs inside a human cell and beheading them (mRNAs) to steal the 5' cap, splicing the cap to virus's own (negative-sense) RNA pieces. Afterwards, with these RNAs as templates, the virus directs the making of now positive-sense RNAs (which can be translated into viral proteins).

The cap-snatching is done by virus own "cap 帽子-dependent endonuclease."
mechanism of action: compare

(e) Shionogi Enters into a License and Collaboration Agreement with Roche for Its Anti-Flu Drug, S-033188. Shionogi & Co, Ltd, Feb 20, 2016.
www.shionogi.eu/media/381353/e160229-roche-188.pdf
(mechanism of action: view graphic only)
(i) S-033188 is s small molecule that inhibits cap-dependent endonuclease, so that even though an influenza virus enters a host cells, it (the virus) is stopped in its track.
(ii) The existing competitors, such as  Oseltamivir (brand name: Tamiflu; made by Roche; by mouth) are a group of small molecules that inhibits viral neuraminidase.
(iii)  S-033188 is effective against influenza virus from fellow humans and bird -- clinical trial against swine influenza virus is not tested yet.