Heterocyclic compounds play a critical role in medicinal chemistry, and many available
drugs contain heterocyclic rings. A six-membered heterocyclic compound, pyridine, showed various
applications, including being an important solvent, reagent, and precursor in agrochemicals and pharmaceuticals.
Due to the increase in drug resistance, there is an apparent medical need to develop new
antiviral agents. Various derivatives of pyridine scaffold display broad biological activities such as
anti-microbial, antiviral, antioxidant, anti-diabetic, anti-cancer, anti-malarial, analgesic, and antiinflammatory
activities. Furthermore, they display psychopharmacological, antagonistic, anti-amoebic
agents, and anti-thrombic activities. Due to the high importance of pyridine derivatives, in the present
review, we tried to collect and classify many pyridine derivatives based on their structures from 2000
to 2020. Pyridine derivatives were classified into two general categories, including pyridine containing
heterocycles and pyridine fused rings. The structure-activity relationship (SAR) and the action mechanism
of derivatives were also investigated. According to the recent studies, these derivatives exhibited
good antiviral activity against different types of viruses such as the human immunodeficiency viruses
(HIV), the hepatitis C virus (HCV), the hepatitis B virus (HBV), respiratory syncytial virus (RSV), and
cytomegalovirus (CMV). These derivatives inhibited viral application with different action mechanism
such as RT inhibition, polymerase inhibition, inhibition of RNase H activity, inhibition of maturation,
inhibition of the viral thymidine kinase, AAK1 (Adaptor-Associated Kinase 1) inhibition, GAK (Cyclin
G-associated kinase) inhibition, inhibition of post-integrational event, inhibition of HDAC6,
CCR5 antagonistic activity, DNA and RNA replication inhibition, gene expression inhibition, cellular
NF-jB signaling pathway and neuraminidase (NA) inhibition, protein synthesis inhibition, and generally
inhibition of viral replication cycle. This paper summarized the past and present results about the
discovery of novel lead compounds with good antiviral activity. Studies exhibited that almost all of the
evaluations were performed by way of in vitro testing. It is necessary to investigate in vivo and clinical
testing for better evaluations in the future. We believe that pyridine derivatives can be used as promising
antiviral agents and more broad investigations in this field need to be performed.