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Applications of the revolving motor
Published in Peixuan Guo, Zhengyi Zhao, Biomotors: Linear, Rotation, and Revolution Motion Mechanisms, 2017
Since viral motors share certain common structures and operation mechanisms, methods of targeting homomeric multisubunit complexes should have general applications in antiviral drug discovery. Homomeric channel proteins, such as the homotetramer M2 proton channel protein, have been shown to be a better target for anti-influenza drugs (Wang et al., 1993). Amantadine and rimantadine inhibit the influenza virus through this mechanism by entering the barrel of the tetrameric M2 channel and blocking proton translocation function (Figure 10.2a) (Philippe et al., 2013). RNA-dependent RNA-polymerase NS5B, which plays an important role in hepatitis C virus (HCV) replication, exists as a homomeric oligomer. NS5B–NS5B intermolecular interaction is essential for both initiation and elongation of RNA synthesis (Lopez-Jimenez et al., 2014). Targeting the oligomeric protein NS5B could also be helpful to delineate new and powerful antiviral strategies (Pi et al., 2015, 2016; Shu et al., 2015).
Current and Future Applications of Diamondoids and Their Derivatives
Published in Sven Stauss, Kazuo Terashima, Diamondoids, 2017
Rimantadine (alpha-methyl-1-adamantane-methylamine hydrochloride) is another adamantane derivative, in addition to amantadine and memantine (see Fig. 4.4). Amantadine (1-adamantanemine hydrochloride) and memantine (displayed in the middle of Fig. 4.4) both show anti-Parkinsonian activity. In the following paragraphs, we treat the case of rimantadine. In 1993, rimantadine, which is the alpha-methyl derivative of amantadine, was approved by the US Food and Drug Administration for the prophylaxis and treatment of influenza A virus (although later studies suggest that the activity against influenza A decreased). Compared to amantadine, rimantadine has a few advantageous properties: It has fewer central nervous and sleep side effects.Its elimination half-life, that is, the time it takes the body to reduce its quantity by half, is about 24 to 36 hours, compared to 12–18 hours for amantadine.It possesses a 10 times higher partition coefficient when compared to amantadine.
Pulmonary complications of bone-marrow and stem-cell transplantation
Published in Philippe Camus, Edward C Rosenow, Drug-induced and Iatrogenic Respiratory Disease, 2010
Bekele Afessa, Andrew D Badley, Steve G Peters
Since severe disease is more likely to occur near the time of transplantation, the procedure should be delayed in patients with respiratory virus infection.32 Immunization with inactivated influenza is recommended. However, response to vaccine is lost for 6 months after transplant, and chronic GVHD is associated with poor response.32 Amantidine or rimantidine prophylaxis may be used to provide partial protection when influenza A activity is detected in the community.32 Although ribavirin is active in vitro against influenza A and B viruses, clinical data are not available.32 Treatment with amantadine or rimantadine is not of benefit if initiated after the development of respiratory failure.33 Oseltamivir may play a beneficial role for therapy and for prophylaxis following confirmed exposure to influenza A and B.34 Pneumonia in patients with influenza infection is associated with 50 per cent mortality.19
Synthesis, characterization, crystal structure, and electrochemical properties of three copper(II) complexes with 3,5-dihalosalicylaldehyde Schiff bases derived from amantadine
Published in Journal of Coordination Chemistry, 2019
Xu-Dong Jin, Han Wang, Xiao-Kang Xie, Jia-Yue Sun, He-Ming Liang
In many countries, amantadine (SymmetrelTM) and rimantadine (FlumadineTM) have been widely used to treat or prevent seasonal influenza as efficacious remedies [14–17]. It can also alleviate Parkinson symptoms [18, 19]. Salicylaldehyde and substituted salicylaldehydes, especially halogenated salicylaldehydes, were used to produce herbicides, insecticides and fungicides [20–22]. As an extension of our previous studies on the electrochemical properties of copper complexes with Schiff bases derived from amantadine or rimantadine [23, 24], we designed and synthesized three copper(II) complexes with the Schiff bases derived from amantadine and 3,5-dihalosalicylaldehydes.
2D-QSAR, 3D-QSAR, molecular docking and ADMET prediction studies of some novel 2-((1H-indol-3-yl)thio)-N-phenyl-acetamide derivatives as anti-influenza A virus
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Mustapha Abdullahi, Adamu Uzairu, Gideon Adamu Shallangwa, Paul Andrew Mamza, Muhammad Tukur Ibrahim
Influenza (A) virus (IAV) infection remains one of the major causes of mortality and morbidity due to respiratory diseases in recent times even with the devastating Covid-19 pandemic [1]. The World Health Organization (WHO) reported about 2–5 million cases of severe illness caused by the ravaging seasonal influenza virus epidemic which resulted in over 500,000 deaths globally [2]. These flu epidemics cause severe respiratory infections in children, adults, the elderly, and individuals with underlying health conditions [3] [4]. Influenza virus neuraminidase (NA) is an enzyme that catalyzes the obliteration of terminal sialic acid residues (sialidase) which aids in liberating new virions formed from the infected cells and circulating to infect the neighboring cells [5]. As such, the NA inhibition can defend the host from being infected and prevent its proliferation [1]. Due to the highly preserved active site structure of neuraminidase [6], it has become an attractive molecular target for the exploration and development of novel anti-influenza inhibitors. Presently, Zanamivir (Relenza™), oseltamivir (Tamiflu™), laninamivir octanoate (Inavir™), and peramivir (Rapivab™) are the four (4) approved neuraminidase inhibitors for influenza treatment [7]. The IAV disease is usually linked to severe symptoms because of the intense genetic diversity characterized by chromosomal mutation between avian and human viruses. Presently, the only two major classes of antiviral medicines against the influenza A virus are inhibitors of M2-ion channel (rimantadine and amantadine) and neuraminidase (zanamivir and oseltamivir) targets that fight against its spreading around the globe. However, most influenza A virus strains have become resistant to these drugs in recent times. There is a lot of concern for the advent of drug resistance effects resulting from the high variability of the influenza virus or respiratory syncytial virus (RSV) [5]. This is because a patient infected with either virus can manifest similar symptoms at an early stage. The discovery of some novel compounds of 2-((1 H-indol-3-yl)thio) acetamide as dual inhibitors against IAV and RSV is a huge milestone for the rapid therapy of these respiratory co-infections. Moreover, the trial and error approach applied in the development of new drugs has been seen to be very tedious, costly, and time-consuming [8].