Antiviral drug design

Amaro RE, Minh DDL, Cheng LS, Lindstrom WM Jr, Olson AJ, Lin J-H, Li WW, McCammon JA (2007) Remarkable loop flexibihty in avian influenza N1 and its implications for antiviral drug design. J Am Chem Soc 129 7764-7765... 

Figure 9.1 The viral infectious unit, or virion, consists of a nucleic acid encased in a protein shell. The various structural components of the virion exhibit differing functional properties and thus afford a variety of targets for antiviral drug design.

Influenza virus sialidase poses a highly attractive target for antiviral drug design due to its prominent position at the surface of the virion and its profound role in viral pathogenesis. Random screening programs identified a number of... 

Perros, M, (2007) CCR5 antagonists for the treatment of HIV infection and aids. Advances in Antiviral Drug Design, 5, 185-212. 

Some of their derivatives have been used as antiviral drugs. Due to their flexible chemistry, they can be exploited to design drug delivery systems and in molecular nanotechnology. In such systems, they can act as a central lipophilic core and different parts like targeting segments, linkers, spacers, or therapeutic agents can be attached to the said central nucleus. Their central core can be functionalized by peptidic and nucleic acid sequences and also by numerous important biomolecules. 

Jean-Marc Sabatier has a Ph.D. and HDR in biochemistry. He is the director of research at the French Centre National de la Recherche Scientifique (CNRS). He heads a research laboratory (ERT 62) entided Engineering of Therapeutic Peptides at the Universite de la Mediterranee, in Marseilles, France. He also holds the position of a senior director (discovery research — peptides) for a public company in Canada. Dr. Sabatier works in the field of animal toxins, and leads the venom peptide group of the International Neuropeptide Society. He also designs immunomodulatory and antiviral drugs, as well as contributes to the field of peptide and protein engineering. He has contributed more than 100 scientific articles, 180 communications, and 43 patents. He is a member of several scientific advisory boards of journals (e.g.. Peptides, Biochemical Journal), and has reviewed articles submitted for publication in more than 30 specialized international journals. 

When designing new chemical entities as putative antivirals, there are seven logical steps in viral biochemistry and replication at which druggable targets suitable for drug design can be identified ... 

All the nearest-neighbor interactions between sialic acid or Neu5Ac2en and the protein are with totally conserved amino acids. Thus an inhibitor designed to bind only to the conserved active-site residues of neuraminidase would inhibit neuraminidase activity across all strains of influenza. This would enable the development of an antiviral drug that would affect the spread of viral replication potentially in three ways, i.e., transport through the protective mucosal layer, desialyation of freshly synthesized viral glycoproteins, and elution of progeny virions from infected cells. 

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