MM3122: Dan takarar jagora don Novel Antiviral magani akan COVID-19

T MPRSS2 muhimmin abu ne da ake son cimmawa wajen samar da magungunan hana kamuwa da cutar COVID-19. MM3122 jagora ne wanda ya nuna sakamako mai kyau a cikin jiki da kuma a cikin samfuran dabbobi.

Ana ci gaba da farautar sabbin magungunan hana ƙwayoyin cuta a kan COVID-19, wata cuta da ta haifar da barna a cikin shekaru 2 da suka gabata kuma ta lalata tattalin arzikin ƙasashe da dama a duniya. Masu karɓar ACE2 da kuma nau'in 2 na transmembrane serine proteases (TMPRSS2) duk suna wakiltar manyan manufofin gano magunguna domin suna sauƙaƙa shigar ƙwayoyin cuta cikin ƙwayoyin huhu ^1. Yankin ɗaurewa na ƙwayoyin cuta na SARS-CoV-2 (RBD) yana manne da mai karɓar ACE2 kuma furotin TMPRSS2 yana taimakawa wajen raba furotin mai girma (S) na ƙwayar, ta haka ne ke fara shigar ƙwayoyin cuta kuma yana taimakawa wajen tserewa daga tsarin garkuwar jiki ^2. Wannan labarin bita zai mayar da hankali kan rawar da TMPRSS2 ke takawa a cikin al'ummar ɗan adam da kuma dalilin da yasa yake gabatarwa a matsayin manufa mai kyau ta magani don haɓaka masu hana da haɓaka MM3122 ³ , wani sabon magani wanda ke aiki a matsayin mai hana TMPRSS2.

TMPRSS2 na cikin dangin serine protease kuma yana da alhakin ayyuka da yawa na cututtuka da na jiki da ke faruwa a jikin ɗan adam. TMPRSS2 yana raba furotin na SARS-CoV-2 Spike kuma yana kunna shi yayin haɗuwar membrane, ta haka yana ƙara shigar ƙwayoyin cuta cikin ƙwayoyin cuta. Nazarin ya danganta bambance-bambancen kwayoyin halitta, bambance-bambancen jinsi da tsarin bayyanar TMPRSS2 tare da saurin kamuwa da tsananin cutar COVID-19 . An nuna cewa ayyukan TMPRSS2 sun fi yawa a cikin yawan mutanen Italiya fiye da takwarorinsu na Gabashin Asiya da Turai wanda ya haifar da mafi girman mace-mace da tsananin cutar COVID-19 a Italiya ^4. Bugu da ƙari, bayyanar TMPRSS2 yana ƙaruwa da shekaru wanda ke sa tsofaffi su fi fuskantar COVID-19 ^5. Wani bincike ya nuna cewa matakan testosterone masu yawa suna da alaƙa da ƙaruwar bayyanar TMPRSS2 ¹ , don haka yana sa maza su fi fuskantar COVID-19 sabanin mata na rukunin tsofaffi. Babban bayyanar TMPRSS2 yana da alaƙa da ci gaban ciwon daji na prostate a cikin maza ⁶.

Ci gaban MM3122 ya dogara ne akan ƙirar magunguna masu ma'ana . Wannan ya kasance na ajin mahaɗan da aka sani da ketobenzothiazoles, waɗanda suka bambanta a tsarin kuma suna nuna ingantaccen aiki akan masu hana ƙwayoyin cuta da aka sani kamar Camostat da Nafamostat. MM3122 yana da IC ₅₀ (rabin matsakaicin yawan hanawa) na 340 pM (picomolar) akan furotin TMPRSS2 da aka sake bayyanawa, da kuma EC ₅₀ na 74 nM wajen hana tasirin cytoopathic da ƙwayar SARS-CoV-2 ta haifar a cikin ƙwayoyin Calu-3 ^3. Dangane da nazarin beraye, MM3122 yana nuna kyakkyawan kwanciyar hankali da aminci na rayuwa kuma yana da rabin rayuwa na awanni 8.6 a cikin jini da awanni 7.5 a cikin kyallen huhu. Waɗannan halaye, tare da ingancinsa a cikin vitro, sun sa MM3122 ya zama ɗan takara mai dacewa don ƙarin kimantawa a cikin jiki , wanda hakan ya haifar da magani mai kyau don maganin COVID-19.

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References:   

1. Seyed Alinaghi S, Mehrtak M, MohsseniPour, M et al. 2021. Lalacewar kwayoyin halittar COVID-19: nazari na yau da kullun na shaidar yanzu. Farashin J Med Res 26, 46 (2021). DOI: https://doi.org/10.1186/s40001-021-00516-8. 

2. Shang J, Wan Y, Luo C et al. 2020. Hanyoyin shigarwa cell na SARS-CoV-2. Abubuwan da aka gabatar na Kwalejin Kimiyya ta Kasa Mayu 2020, 117 (21) 11727-11734; DOI: https://doi.org/10.1073/pnas.2003138117. 

3. Mahoney M. et al 2021. A labari aji na TMPRSS2 hanawa da karfi toshe SARS-CoV-2 da MERS-CoV hoto ko bidiyo mai zagaya yanar gizo da sauri shigarwa da kuma kare mutum epithelial huhu Kwayoyin. PNAS Oktoba 26, 2021 118 (43) e2108728118; DOI: https://doi.org/10.1073/pnas.2108728118 

4. Choudhary S, Sreenivasulu K..  Ann Lab Med 2021; 41:129-138. DOI: https://doi.org/10.3343/alm.2021.41.2.129 

5. Peng J, Sun J, Zhao J da al., 2021. Shekaru da bambancin jinsi a cikin ACE2 da TMPRSS2 maganganu a cikin kwayoyin epithelial na baka. J Transl Med 19, 358 (2021). DOI: https://doi.org/10.1186/s12967-021-03037-4 

6. Sarker J, Das P, Sarker S. . 2021, Labarin ID 2, shafuka 2, 2021. DOI: https://doi.org/10.1155/2021/2706789 

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