Mammalian cells have evolved a unique strategy to protect themselves against oxidative damage induced by reactive oxygen species (ROS). Especially, two transcription factors, nuclear factor erythroid 2p45‐related factor 2 (Nrf2) and peroxisome proliferator‐activated receptor γ (PPARγ), have been shown to play key roles in establishing this cellular antioxidative defense system. Recently, several researchers reported ameliorating effects of pharmacological activators for these Nrf2 and PPARγ pathways on the progression of various metabolic disorders and drug‐induced organ injuries by oxidative stress. In this review, general features of Nrf2 and PPARγ pathways in the context of oxidative protection will be summarized first. Then, a number of successful applications of natural and synthetic Nrf2 and PPARγ activators to the alleviation of pathological and drug‐related oxidative damage will be discussed later.

Virus‐induced oxidative stress plays a critical role in the viral life cycle as well as the pathogenesis of viral diseases. In response to reactive oxygen species (ROS) generation by a virus, a host cell activates an antioxidative defense system for its own protection. Particularly, a nuclear factor erythroid 2p45‐related factor 2 (Nrf2) pathway works in a front‐line for cytoprotection and detoxification. Recently, a series of studies suggested that a group of clinically relevant viruses have the capacity for positive and negative regulations of the Nrf2 pathway. This virus‐induced modulation of the host antioxidative response turned out to be a crucial determinant for the progression of several viral diseases. In this review, virus‐specific examples of positive and negative modulations of the Nrf2 pathway will be summarized first. Then a number of successful genetic and pharmacological manipulations of the Nrf2 pathway for suppression of the viral replication and the pathogenesis‐associated oxidative damage will be discussed later. Understanding of the interplay between virus‐induced oxidative stress and antioxidative host response will aid in the discovery of potential antiviral supplements for better management of viral diseases.

Virus entry into a susceptible host cell is the first step in the formation of all viral diseases. Controlling viral infections by disrupting viral entry is advantageous for antibody-mediated neutralization by the host’s immune system and as a preventive and therapeutic antiviral strategy. Recently, several plant-derived carbohydrate-binding proteins (lectins) have emerged as a new class of antiviral biologics by taking advantage of a unique glycosylation pattern only found on the surface of viruses. In particular, a red algae-derived griffithsin (GRFT) protein has demonstrated superior in vitro and in vivo antiviral activity with minimum host toxicity against a variety of clinically relevant, enveloped viruses. This review examines the structural characteristics of GRFT, focusing on its carbohydrate-binding capability. Its in vitro antiviral profiles against human immunodeficiency virus (HIV) are also discussed followed by a description of the results from a combination study using anti-HIV drugs. The results of several studies regarding its novel antiviral mechanism of action are provided in conjunction with an explanation of viral resistance profiles to GRFT. In addition, its in vitro and in vivo host toxicity profiles are summarized with its pharmacokinetic behavior using in vivo efficacy study results. Also, a large-scale production and formulation strategy, as well as a drug delivery strategy, for GRFT as a new class of broad-spectrum microbicides is discussed. Finally, results from two ongoing clinical studies examining GRFT’s effects on viruses are presented.

From its unexpected discovery as a bacterial adaptive immune system to its countless applications as one of the most versatile gene-editing tools, the CRISPR/Cas9 system has revolutionized every field of life science. Virology is no exception to this ever-growing list of CRISPR/Cas9-based applications. Direct manipulation of a virus genome by CRISPR/Cas9 has enabled a systematic study of cis-elements and trans-elements encoded in a virus genome. In addition, this virus genome-specific mutagenesis by CRISPR/Cas9 was further funneled into the development of a novel class of antiviral therapy targeting many incurable chronic viral infections. In this review, a general concept on the CRISPR/Cas9-based antiviral strategy will be described first. To understand the current status of the CRISPR/Cas9-based antiviral approach, a series of recently published antiviral studies involving CRISPR/Cas9-mediated control of several clinically-relevant viruses including human immunodeficiency virus, hepatitis B virus, herpesviruses, human papillomavirus, and other viruses will be presented. Lastly, the potential challenge and future prospect for successful clinical translation of this CRISPR/Cas9-based antiviral method will be discussed.

The coronavirus disease 2019 (COVID-19) pandemic has had irreversible and devastating impacts on every aspect of human life. To better prepare for the next similar pandemic, a clear understanding of coronavirus biology is a prerequisite. Nevertheless, the high-risk nature of the causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), requires the use of a cumbersome biosafety level-3 (BSL-3) confinement facility. To facilitate the development of preventive and therapeutic measures against SARS-CoV-2, one of the endemic strains of low-risk coronaviruses has gained attention as a useful research alternative: human coronavirus OC43 (HCoV-OC43). In this review, its history, classification, and clinical manifestations are first summarized. The characteristics of its viral genomes, genes, and evolution process are then further explained. In addition, the host factors necessary to support the life cycle of HCoV-OC43 and the innate, as well as adaptive, immunological responses to HCoV-OC43 infection are discussed. Finally, the development of in vitro and in vivo systems to study HCoV-OC43 and its application to the discovery of potential antivirals for COVID-19 by using HCoV-OC43 models are also presented. This review should serve as a concise guide for those who wish to use HCoV-OC43 to study coronaviruses in a low-risk research setting.