Triazavirín by mohol byť novovu nádejou v súboji s koronavírusom 2 vyvolávajúcim ťažký akútny respiračný syndróm (SARS-CoV-2)

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Autoři: Ivan Malík ^1,2; Jozef Čižmárik ²; Mária Pecháčová ²; Gustáv Kováč ¹; Lucia Hudecova ¹;
Působiště autorů: Institute of Chemistry, Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Slovak Medical University in Bratislava, Slovak Republic ¹; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava, Slovak Republic ²
Vyšlo v časopise: Čes. slov. Farm., 2021; 70, 18-25
Kategorie: Rewiev article
doi: https://doi.org/https://doi.org/10.5817/CSF2021-1-18

Souhrn

Od začiatku pandémie vysokoinfekčného ochorenia COVID-19 (Coronavirus Disease-19), ktoré je spôsobené koronavírusom 2 vyvolávajúcim ťažký akútny respiračný syndróm (Severe Acute Respiratory Syndrome Coronavirus 2; SARS-CoV-2), bol celosvetovo registrovaný veľký počet klinických štúdií, v ktorých sú hodnotené tisícky liečiv. Stratégia reprofilizácie liečiv, t.j. utilizácia liečiv, ktorých terapeutické použitie už bolo schválené v inej indikácii, získa čas a zníži náklady na liečbu dovtedy, kým budú lekárom a pacientom k dispozícii nové (relevantné) terapeutické alternatívy. Z tohto dôvodu je proti SARS-CoV-2 hodnotených aj mnoho zlúčenín, ktoré sú schválené alebo experimentálne používané v liečbe infekcií zapríčinených koronavírusom 1 vyvolávajúcim ťažký akútny respiračný syndróm (Severe Acute Respiratory Syndrome Coronavirus 1), koronavírusom vyvolávajúcim stredovýchodný respiračný syndróm (Middle East Respiratory Syndrome Coronavirus), vírusom ľudskej imunodeficiencie typu 1 (Human Immunodeficiency Virus type 1) alebo vírusmi chrípky (Influenza viruses). Triazavirín (TZV) je netoxickým širokospektrálnym antivirotikom, ktoré efektívne pôsobí proti rôznym kmeňom chrípky antigénneho typu A (Influenza Virus A, Orthomyxoviridae), t.j. prasacej chrípke (H1N1 alebo H3N2), vtáčej chrípke (H5N1, H5N2, H9N2 alebo proti vysokopatogénnemu kmeňu H7N3), kmeňom chrípky antigénneho typu B (Influenza Virus B, Orthomyxoviridae), respiračnému syncyciálnemu vírusu (Orthopneumovirus, Pneumoviridae), vírusu kliešťovej encefalitídy (Flavivirus, Flaviviridae), vírusu západonílskej horúčky (Flavivirus, Flavaviridae), vírusu horúčky Rift Valley (Phlebovirus, Buny-aviridae) a aj herpesvírusom (Simplexviruses, Herpesviridae). V kontexte terapie ochorenia COVID-19 táto zlúčenina pravdepodobne redukovala zápalové reakcie, a takto limitovala poškodenie vitálnych orgánov a oddialila eventualitu terapeutickej podpory. Výpočtové metódy in silico tiež indikovali relatívne uspokojivé väzbové afinity tohto ligandu k štruktúrnym (E)- a (S)-proteínom, neštruktúrnej proteáze podobnej 3-chymotrypsínu (3-CL^pro) SARS-CoV-2 a aj receptoru ľudí, enzýmu-2 konvertujúcemu angiotenzín-I (ACE-2). Interakcie medzi TZV a vírusovými štruktúrami alebo ACE-2-receptorom pre SARS-CoV-2 by mohli efektívne blokovať vstup patogéna do hostiteľskej bunky a tiež jeho intracelulárnu replikáciu. Sľubné terapeutické schémy pre liečbu COVID-19-pozitívnych pacientov by mohli spočívať vo vhodnej kombinácii inhibítora fúzie membrán (napr. umifenoviru) s inhibítorom syntézy a replikácie vírusovej RNA (TZV).

Klíčová slova:

SARS-CoV-2 – COVID-19 – reprofilizácia liečiv – triazavirín – štruktúrne proteíny – proteáza podobná 3-chymotrypsínu – ACE-2

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