ABSTRACT
INTRODUCTION: GSK has developed a two-dose adjuvanted recombinant zoster vaccine (Shingrix, RZV) to protect people aged ≥50 years (50+) against herpes zoster (HZ) and its complications. RZV showed >90% efficacy against HZ, sustained over 4 years of follow-up, in all studied age groups. AREAS COVERED: This article reviews the scientific rationale underlying the design of RZV; the clinical evidence demonstrating immunogenicity, safety, and efficacy in persons 50+; and the public health implications and cost-effectiveness. EXPERT COMMENTARY: A decline in varicella zoster virus (VZV) immunity is associated with increased risk of HZ in adults 50+ and immunocompromised individuals. RZV was designed to restore levels of anti-VZV cellular and humoral immunity to prevent VZV reactivation. RZV includes the recombinant gE glycoprotein antigen, and Adjuvant System AS01B which promotes cellular and antibody responses. In two Phase III studies in subjects aged 50+ and 70+ years, RZV efficacy against HZ compared to placebo was >90% and ≥89% against post-herpetic neuralgia (PHN). RZV is expected to dramatically impact HZ morbidity including its complications, and associated health-care costs. In the US population aged 50+ years, vaccination with RZV can be cost-effective compared to no vaccination and cost-saving compared to the currently available live-attenuated HZ vaccine (Zostavax, Merck).
Subject(s)
Herpes Zoster Vaccine/administration & dosage , Herpes Zoster/prevention & control , Neuralgia, Postherpetic/prevention & control , Adjuvants, Immunologic/administration & dosage , Aged , Animals , Cost-Benefit Analysis , Herpes Zoster/complications , Herpes Zoster/immunology , Herpes Zoster Vaccine/adverse effects , Herpes Zoster Vaccine/immunology , Humans , Immunocompromised Host , Middle Aged , Public HealthABSTRACT
A series of 9 quinolines and 18 styrylquinolines was evaluated for the drugs' in vitro antileishmanial activities and cytotoxicities. The 7-aroylstyrylquinoline scaffold appeared to be the most promising one, with the most interesting compound, no. 35, exhibiting a 50% inhibitory concentration (IC(50)) of 1.2 µM and a selectivity index value of 121.5. Compound 35 was 10-fold and 8-fold more active than miltefosine and sitamaquine, the reference compounds, with selectivity indexes 607-fold and 60-fold higher, respectively.
Subject(s)
Leishmania donovani/drug effects , Quinolines/pharmacology , Trypanocidal Agents/pharmacology , Inhibitory Concentration 50 , Molecular Structure , Structure-Activity RelationshipABSTRACT
Novel variants of HIV-1 replication inhibitors of the styrylquinoline class harboring aroyl/acyl group at the C-7 position have been synthesized. In sharp contrast with styrylquinolines bearing a carboxylic acid group at C-7, these compounds proved to be inactive toward HIV-1 integrase in in vitro assays.
Subject(s)
Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacology , HIV-1/drug effects , HIV-1/physiology , Quinolines/chemistry , Quinolines/pharmacology , Virus Replication/drug effects , Acylation , Anti-HIV Agents/chemistry , Anti-HIV Agents/toxicity , HIV Integrase/metabolism , Inhibitory Concentration 50 , Molecular Structure , Quinolines/chemical synthesis , Quinolines/toxicity , Structure-Activity RelationshipABSTRACT
A novel series of HIV-1 integrase inhibitors was synthesized and tested in both in vitro and ex vivo assays. These inhibitors are featured by the presence of a quinoline subunit and an ancillary aromatic ring linked by functionalized spacers such as amide, hydrazide, urea and 1-hydroxyprop-1-en-3-one moiety. Amide derivatives are the most promising ones and could serve as leads for further developments.
