| | efavirenz uk - efavirenz use during pregnancy - This review highlights ten 窶徂ot topics窶 in current antiviral research: (i) new nucleoside derivatives (i.e., PSI-352938) showing high potential as a direct antiviral against hepatitis C virus (HCV); (ii) cyclopropavir, which should be further pursued for treatment of human cytomegalovirus (HCMV) infections; (iii) North-methanocarbathymidine (N-MCT), with a N-locked conformation, showing promising activity against both ﾎｱ- and ﾎｳ-herpesviruses; (iv) CMX001, an orally bioavailable prodrug of cidofovir with broad-spectrum activity against DNA viruses, including polyoma, adeno, herpes, and pox; (v) favipiravir, which is primarily pursued for the treatment of influenza virus infections, but also inhibits the replication of other RNA viruses, particularly (-)RNA viruses such as arena, bunya, and hanta; (vi) newly emerging antiarenaviral compounds which should be more effective (and less toxic) than the ubiquitously used ribavirin; (vii) antipicornavirus agents in clinical development (pleconaril, BTA-798, and V-073); (viii) natural products receiving increased attention as potential antiviral drugs; (ix) antivirals such as U0126 targeted at specific cellular kinase pathways e., mitogen extracellular kinase (MEK)], showing activity against influenza and other viruses; and (x) two structurally unrelated compounds (i.e., LJ-001 and dUY11) with broad-spectrum activity against virtually all enveloped RNA and DNA viruses. ﾂｩ 2012 Wiley Periodicals, Inc. Med. Res. Rev., 00, No. 0, 1窶34, 2012 to The recent cocrystallization of the foamy virus integrase DNA complex or intasome with both RAL and EVG (Hare et al. 2010) corroborates the biochemical mechanism and provides a structural basis for understanding the unique breadth of antiviral activity that has been observed for InSTIs across all HIV-1 subtypes as well as other retroviruses, such as HIV-2 and XMRV (Fig. 5) (Maignan et al. 1998; Damond et al. 2008; Shimura et al. 2008; Van Baelen et al. 2008; Garrido et al. 2010; Singh et al. 2010). In the cocrystal structure, the general architecture and amino acids within the active site of the foamy virus intasome are highly conserved with other retroviral integrases, as are the immediate surrounding interactions with InSTIs. The common mechanism of action and conserved binding mode for InSTIs also has important implications for understanding resistance to the class. Mutations that engender resistance to InSTIs almost always map within the integrase active site near the amino acid residues that coordinate the essential magnesium cofactors (Hazuda et al. 2004a; Hare et al. 2010). Thus, these mutations have deleterious effects on enzymatic function and viral replicative capacity (Marinello et al. 2008; Quercia et al. 2009). In clinical studies, resistance to Raltegravir is associated with three independent pathways or sets of mutations in the integrase gene, as defined by primary or signature mutations at Y143, N155, or Q148 (Fransen et al. 2009). These primary mutations are generally observed with specific secondary mutations; for N155(H) these include E92Q, V151L, T97A, G163R, and L74M, whereas for Q148(K/R/H), G140S/A and E138K are common. Significant cross resistance is observed among the InSTIs almost regardless of the primary/secondary mutation sets (Goethals et al. 2008; Marinello et al. 2008). 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