PMID- 32114034
OWN - NLM
STAT- MEDLINE
DCOM- 20210111
LR  - 20210111
IS  - 1872-9096 (Electronic)
IS  - 0166-3542 (Linking)
VI  - 176
DP  - 2020 Apr
TI  - Acyclovir, cidofovir, and amenamevir have additive antiviral effects on herpes 
      simplex virus TYPE 1.
PG  - 104754
LID - S0166-3542(19)30600-X [pii]
LID - 10.1016/j.antiviral.2020.104754 [doi]
AB  - Herpes simplex virus-1 (HSV-1) affects a large portion of the global population 
      and has been shown to cause more severe symptoms in immunocompromised patients. 
      It is in immunocompromised populations that HSV-1 has shown to have higher rates 
      of resistance to the most commonly used antiherpetics, such as 
      acyclovir/valacyclovir/penciclovir/famciclovir. The development of drug 
      resistance has forced research into new antiherpetic therapies, including 
      combination drug therapies. One potential complication of multidrug therapies is 
      the existence of drug-drug interactions; as more drugs are used in the therapy, 
      those interactions tend to become more complicated. This study tested the 
      combination of acyclovir/cidofovir/amenamevir, the last drug being a new 
      antiherpetic that targets the helicase-primase complex to prevent replication of 
      viral DNA, for multidrug intervention. We used the design of experiments (DOE) 
      function in Minitab to analyze the drug-drug interactions in their ability to 
      inhibit growth of HSV-1. The DOE software was unable to detect any significant 
      drug-drug interactions among these three antiherpetics as dosed. This would imply 
      that these drugs could be used in combination to suppress viral replication 
      without synergistic or antagonistic effects. This study shows that this therapy 
      holds potential for further study and that DOE software is a potentially useful 
      tool for determining complex drug-drug interactions.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Greeley, Zachary W
AU  - Greeley ZW
AD  - Towson University Herpes Virus Lab, Department of Biological Sciences, Towson 
      University, Towson, MD, 21252, USA; Oncology Analytical Pharmacology Core, The 
      Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
FAU - Giannasca, Nicholas J
AU  - Giannasca NJ
AD  - Towson University Herpes Virus Lab, Department of Biological Sciences, Towson 
      University, Towson, MD, 21252, USA.
FAU - Porter, Morgan J
AU  - Porter MJ
AD  - Towson University Herpes Virus Lab, Department of Biological Sciences, Towson 
      University, Towson, MD, 21252, USA.
FAU - Margulies, Barry J
AU  - Margulies BJ
AD  - Towson University Herpes Virus Lab, Department of Biological Sciences, Towson 
      University, Towson, MD, 21252, USA; Department of Pharmacology and Molecular 
      Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, 
      USA; Molecular Biology, Biochemistry, and Bioinformatics Program, Towson 
      University, Towson, MD, 21252, USA. Electronic address: bjmarg@alum.mit.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200227
PL  - Netherlands
TA  - Antiviral Res
JT  - Antiviral research
JID - 8109699
RN  - 0 (ASP2151)
RN  - 0 (Antiviral Agents)
RN  - 0 (Oxadiazoles)
RN  - JIL713Q00N (Cidofovir)
RN  - X4HES1O11F (Acyclovir)
SB  - IM
MH  - Acyclovir/*pharmacology
MH  - Animals
MH  - Antiviral Agents/*pharmacology
MH  - Chlorocebus aethiops
MH  - Cidofovir/*pharmacology
MH  - Drug Resistance, Viral
MH  - Drug Synergism
MH  - Herpesvirus 1, Human/*drug effects/physiology
MH  - Inhibitory Concentration 50
MH  - Oxadiazoles/*pharmacology
MH  - Vero Cells
MH  - Virus Replication/*drug effects
OTO - NOTNLM
OT  - Acyclovir
OT  - Amenamevir
OT  - Cidofovir
OT  - Combined drug therapy
OT  - Design of experiment
OT  - HSV-1
COIS- Declaration of competing interest The authors declare no conflict of interest in 
      this work.
EDAT- 2020/03/03 06:00
MHDA- 2021/01/12 06:00
CRDT- 2020/03/02 06:00
PHST- 2019/10/18 00:00 [received]
PHST- 2020/02/19 00:00 [revised]
PHST- 2020/02/24 00:00 [accepted]
PHST- 2020/03/03 06:00 [pubmed]
PHST- 2021/01/12 06:00 [medline]
PHST- 2020/03/02 06:00 [entrez]
AID - S0166-3542(19)30600-X [pii]
AID - 10.1016/j.antiviral.2020.104754 [doi]
PST - ppublish
SO  - Antiviral Res. 2020 Apr;176:104754. doi: 10.1016/j.antiviral.2020.104754. Epub 
      2020 Feb 27.