New small-molecule drug design strategies for fighting resistant influenza A

Abstract

Influenza A virus is the major cause of seasonal or pandemic flu worldwide. Two main treatment strategies–vaccination and small molecule anti-influenza drugs are currently available. As an effective vaccine usually takes at least 6 months to develop, anti-influenza small molecule drugs are more effective for the first line of protection against the virus during an epidemic outbreak, especially in the early stage. Two major classes of anti-influenza drugs currently available are admantane-based M2 protein blockers (amantadine and rimantadine) and neuraminidase (NA) inhibitors (oseltamivir, zanamivir, and peramivir). However, the continuous evolvement of influenza A virus and the rapid emergence of resistance to current drugs, particularly to amantadine, rimantadine, and oseltamivir, have raised an urgent need for developing new anti-influenza drugs against resistant forms of influenza A virus. In this review, we first give a brief introduction of the molecular mechanisms behind resistance, and then discuss new strategies in small-molecule drug development to overcome influenza A virus resistance targeting mutant M2 proteins and neuraminidases, and other viral proteins not associated with current drugs.

8‐Hydroxyquinoline‐2‐Carboxanilides as Antiviral Agents Against Avian Influenza Virus

“…The influenza disease caused by infection with the highly pathogenic avian influenza H5N1 virus is one of the most devastating zoonotic viral infectious diseases affecting humans worldwide. At present, only two classes of antiviral drugs, M2 ion channel blockers and neuraminidase inhibitors, are approved for the prevention and treatment of influenza virus infections, but their utility has been limited by their low effectiveness in killing the virus, their side effects and the rapid emergence of drug‐resistant viral strains . Although a number of different classes of natural compounds have been studied for their anti‐H5N1 activity, no quinolone alkaloids have been investigated as agents against avian influenza .…”

Levels of Antiviral Therapy

“…A wide variety of biologically active compounds was found in the plants growing on the territory of Kazakhstan. It's possible to obtain the new highly active drugs with the ability to block a variety of viruses from such plants, including those that are resistant to existing commercial chemical preparations from similar preparations which combine immunostimulatory and antiviral properties can be recommended for the treatment and prevention of infectious diseases associated with immunodeficiency, including influenza, HIV, hepatitis C and others [38][39][40].…”

Designing and screening of universal drug from neem (Azadirachta indica) and standard drug chemicals against influenza virus nucleoprotein

“…Ten previously reported drugs included in the database were: Nucleozin; (+)-( S )-2-(6-methoxynaphthalen-2-yl)-propanoic acid [Naproxen]; 1H-1,2,3-triazole-4-carboxamide [CBX]; AGN-PC-09RM4KT; 4-(2-chloro-4-nitrophenyl)piperazin-1-yl][3-(2-chloropyridin-3-yl)-5-methyl-1,2-oxazol-4-yl]methanone [OMM]; 4-(5-bromanyl-3-methyl-pyridin-2-yl)piperazin-1-yl]-[3-(2-chlorophenyl)-5-methyl-1,2-oxazol-4-yl]methanone [OMS]; 4-(2-chloro-4-nitrophenyl)piperazin-1-yl][3-(2-methoxyphenyl)-5-methyl-1,2-oxazol-4-yl]methanone [LGH]; N-[4-chloranyl-5-[4-[[3-(2-methoxyphenyl)-5-methyl-1,2-oxazol-4-yl]carbonyl]piperazin-1-yl]-2-nitro-phenyl]furan-2-carboxamide [BMS-885986]; N-[4-chloranyl-5-[4-[[3-(2-methoxyphenyl)-5-methyl-1,2-oxazol-4-yl]carbonyl]piperazin-1-yl]-2-nitro-phenyl]pyridine-2-carboxamide [BMS-885838]; and N-[4-chloranyl-5-[4-[[3-(2-methoxyphenyl)-5-methyl-1,2-oxazol-4-yl]carbonyl]piperazin-1-yl]-2-nitro-phenyl]thiophene-2-carboxamide [BMS-883559] [7, 15, 16]. These databases were saved in .mdb format and were further used for docking against the target receptor protein.…”