In vitro evaluation of current and novel antivirals in combination against human cytomegalovirus

Antiviral Research
M Shea O'BrienBrian G Gentry

Abstract

Human cytomegalovirus (HCMV) can cause severe disease in patients with compromised or immature immune systems. Currently approved pharmacotherapies for the treatment of systemic HCMV infections [ganciclovir (GCV), cidofovir (CDV), foscarnet] are limited by a high incidence of adverse effects and/or the development of drug resistance. Given that many of these drugs have the same viral target (HCMV-encoded DNA polymerase), cross-resistance is relatively common. The primary means to combat drug resistance is combination pharmacotherapy using therapeutics with different molecular mechanisms of action with the expectation that those combinations result in an additive or synergistic enhancement of effect; combinations that result in antagonism can, in many cases, be detrimental to the outcome of the patient. We therefore tested select combinations of approved (GCV, CDV, letermovir (LMV)) and experimental (brincidofovir (BCV), cyclopropavir (CPV), maribavir (MBV), BDCRB) drugs with the hypothesis that combinations of drugs with different and distinct molecular mechanisms of action will produce an additive and/or synergistic enhancement of antiviral effect against HCMV in vitro. Using MacSynergy II (a statistical package that measures ...Continue Reading

Citations

Mar 9, 2019·Current Pharmaceutical Biotechnology·Daniele Z RechenchoskiRosa E C Linhares
Jan 26, 2020·Current Hematologic Malignancy Reports·Morgan Hakki
Nov 17, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Hannah N Imlay, Daniel R Kaul
May 6, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yuzhen GaoYouming Zhang
Jun 4, 2019·Current Opinion in Organ Transplantation·Camille N Kotton

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