New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections

• Published in: Chemistry, an Asian journal Vol. 14; no. 22; pp. 3962 - 3968
• Main Author: De Clercq, Erik
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 18-11-2019; John Wiley and Sons Inc
• Subjects: Adenine - analogs & derivatives; Adenine - pharmacology; Adenine - therapeutic use; Amides - chemistry; Amides - metabolism; Amides - pharmacology; Amides - therapeutic use; Antiretroviral drugs; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; antivirals; Base Pairing; Chemistry; Cyano groups; ebola; Ebolavirus - drug effects; Fever; Guanine - analogs & derivatives; Guanine - pharmacology; Guanine - therapeutic use; hemorrhagic fever viruses; Hemorrhagic Fevers, Viral - drug therapy; Humans; Minireview; Minireviews; nucleoside analogues; Nucleosides; Nucleotides - chemistry; Nucleotides - therapeutic use; Phosphoric Acids - chemistry; Phosphoric Acids - therapeutic use; Pyrazines - chemistry; Pyrazines - metabolism; Pyrazines - pharmacology; Pyrazines - therapeutic use; Triazines - chemistry; Triazines - therapeutic use; Uracil; Viruses; nucleoside analogues; antivirals; ebola; hemorrhagic fever viruses
• ISSN: 1861-4728; 1861-471X
• DOI: 10.1002/asia.201900841

Eight different compounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/or other hemorrhagic fever virus (HFV) infections. They can be considered as either (i) adenine analogues (3‐deazaneplanocin A, galidesivir, GS‐6620 and remdesivir) or (ii) guanine analogues containing the carboxamide entity (ribavirin, EICAR, pyrazofurin and favipiravir). All eight owe their mechanism of action to hydrogen bonded base pairing with either (i) uracil or (ii) cytosine. Four out of the eight compounds (galidesivir, GS‐6620, remdesivir and pyrazofurin) are C‐nucleosides, and two of them (GS‐6620, remdesivir) also contain a phosphoramidate part. The C‐nucleoside and phosphoramidate (and for the adenine analogues the 1′‐cyano group as well) may be considered as essential attributes for their antiviral activity.
It is all about potential: Eight different compounds, four adenine analogues (3‐deazaneplanocin A, galidesivir, GS‐6620 and remdesivir) and four guanine analogues containing the carboxamide entity (ribavirin, EICAR, pyrazofurin and favipiravir) can be considered as potential drug candidates for the treatment of Ebola virus and/or other hemorrhagic fever virus infections.