The need for new antiviral agents

Abstract

Population density and immune status, vectors and virulence of infection, nutritional status, sanitation, genetic susceptibility and medical management of cases, are important factors influencing the incidence and/or severity of virus infections. Thus, the prevalence and clinical importance of virus infections and the need for antiviral drugs differ from place to place and from time to time. National and World Health Statistics of notifications of disease give some index of the incidence of infections but not all virus infections are notifiable. Such statistics can be misleading also through failures to notify from sloth on the part of the physician or, in the absence of pathognomonic symptoms or signs, from errors in diagnosis. Any assessment of the need for new antiviral drugs should consider the availability, safety, effectiveness and cost of alternative measures, including prevention of spread of infection by control of vectors, immunization by use of viral vaccines, or treatment with existing antiviral drugs. Early start of treatment of acute virus infections with existing drugs gives the best results and, where the clinical diagnosis is uncertain, accurate rapid virus diagnosis is of paramount importance. Many virus infections are asymptomatic or of trivial importance and without sequelae. However, new or improved antiviral drugs are needed for the prevention and/or treatment of a number of significant conditions caused by viruses which are not at present adequately controlled. These include upper and lower respiratory tract infections, influenza, chronic hepatitis, gastroenteritis, infectious mononucleosis, measles, rabies, haemorrhagic fevers and warts. Furthermore, such drugs might prove of therapeutic value in the prevention or treatment of virus-associated tumours, such as hepatoma, nasopharyngeal carcinoma, Burkitt's lymphoma, Kaposi's sarcoma and possibly carcinoma of the cervix.

A three-dimensional model to analyze drug-drug interactions

“…Although there is a need for continued development of new antiviral agents, the use of combinations of presently existing antiviral drugs is becoming increasingly important for a number of reasons (Freestone, 1985). For example, the use of drug combinations reduces the possibility of selecting drug resistant mutants.…”

Antiherpesvirus Activity of the Combination of 5-iodo-2′-deoxycytidine with methotrexate: Anin vitroandin vivoStudy

“…Most of these compounds derive their specificity from the preferential inhibition of virus-encoded enzymes present in infected cells (McKinley and Rossman, 1989;Prusoff et el., 1985); however, their usefulness is limited by the degree to which they concomitantly affect uninfected cells. Treatment with combinations of antiviral agents is generally thought to minimize drug resistance (Freestone, 1985) and should offer increased selectiVity and efficacy if the component drugs inhibit different metabolic pathways (Prichard et al, 1993a,b).…”

Antivirals in medical biodefense

“…The crucial role of a well-organized public health system and classic quarantine approaches was demonstrated in the recent Ebola outbreaks in West-and Central Africa. However, the need for new antiviral agents had generally been recognized and been reviewed by David Freestone as early as 1985 [47]. While many virus infections are asymptomatic, new or improved antiviral drugs are needed for the prevention and/or treatment of a number of significant conditions caused by viruses which at present cannot be controlled by alternative measures, including vector control, immunization and treatment with existing antiviral drugs.…”