Broad-Spectrum Antiviral Activity of 3D8, a Nucleic Acid-Hydrolyzing Single-Chain Variable Fragment (scFv), Targeting SARS-CoV-2 and Multiple Coronaviruses In Vitro

Lee, Gunsup; Budhathoki, Shailesh; Lee, Geum Young; Oh, Kwang Ji; Ham, Yeon Kyoung; Kim, Young Jun; Lim, Ye Rin; Hoang, Phuong Thi; Lee, Yong-Jun; Lim, Seok Won; Kim, Jun Mo; Cho, Seungchan; Kim, Tai Hyun; Song, Jin Won; Lee, Sukchan; Kim, Won Keun

doi:10.3390/v13040650

Cited by 8 publications

(4 citation statements)

References 44 publications

(67 reference statements)

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“…Single-stranded variable fragment (scFv) is a catalytic antibody with broad-spectrum antiviral activity against DNA and RNA viruses due to its nucleic acid hydrolysis properties. Lee evaluated the antiviral activity of the scFv 3D8 against SARS-CoV-2 and other coronaviruses in VeroE6 cell culture [ 160 ]. It was found that 3D8 inhibited the replication of SARS-CoV-2, human coronavirus OC43 (HCoV-OC43) and porcine epidemic diarrhea virus (PEDV).…”

Section: Catalytic Antibodies That Inhibit New Coronavirus Infectionmentioning

confidence: 99%

“…The preventive and therapeutic effects of catalytic antibody 3D8 against SARS-CoV-2 in VeroE6 cells were demonstrated. Immunoblotting and plaque analysis showed that the nucleoprotein and infected particles of coronavirus decreased in the cells treated with 3D8 [ 160 ]. These data indicate that 3D8 has broad-spectrum antiviral activity against SARS-CoV-2 and other coronaviruses [ 160 ].…”

Section: Catalytic Antibodies That Inhibit New Coronavirus Infectionmentioning

confidence: 99%

“…Immunoblotting and plaque analysis showed that the nucleoprotein and infected particles of coronavirus decreased in the cells treated with 3D8 [ 160 ]. These data indicate that 3D8 has broad-spectrum antiviral activity against SARS-CoV-2 and other coronaviruses [ 160 ]. Therefore, it can be considered a potential antiviral strategy against SARS-CoV-2 and zoonotic coronavirus.…”

Section: Catalytic Antibodies That Inhibit New Coronavirus Infectionmentioning

confidence: 99%

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Catalytic Antibodies: Design, Expression, and Their Applications in Medicine

Zhao

Chen

et al. 2022

Appl Biochem Biotechnol

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Catalytic antibodies made it feasible to develop new catalysts, which had previously been the subject of research. Scientists have discovered natural antibodies that can hydrolyze substrates such as nucleic acids, proteins, and polysaccharides during decades of research, as well as several ways of producing antibodies with specialized characteristics and catalytic functions. These antibodies are widely used in chemistry, biology, and medicine. Catalytic antibodies can continue to play a role and even fully prevent the emergence of autoimmune disorders, especially in the field of infection and immunity, where the process of its occurrence and development often takes a long time. In this work, the development, design and evolution methodologies, and the expression systems and applications of catalytic antibodies, are discussed. Trial registration: not applicable.

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Section: Catalytic Antibodies That Inhibit New Coronavirus Infectionmentioning

confidence: 99%

Section: Catalytic Antibodies That Inhibit New Coronavirus Infectionmentioning

confidence: 99%

Section: Catalytic Antibodies That Inhibit New Coronavirus Infectionmentioning

confidence: 99%

See 1 more Smart Citation

Catalytic Antibodies: Design, Expression, and Their Applications in Medicine

Zhao

Chen

et al. 2022

Appl Biochem Biotechnol

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“…Moreover, 3D8 scFv has intrinsic nucleic acid hydrolyzing activity in a sequence independent manner [ 26 ]. Many previous studies have identified 3D8 scFv antiviral effect against IAV, the classic swine fever virus, human herpes simplex virus, pseudorabies virus, and multiple corona viruses [ 26 , 27 , 28 , 29 , 30 ]. While other flu drugs directed to the protein level (e.g, Oseltamivir) were ineffective on the drug resistant strains, alternative antiviral drugs have been developed to replace Oseltamivir.…”

Section: Introductionmentioning

confidence: 99%

A Therapeutically Active Minibody Exhibits an Antiviral Activity in Oseltamivir-Resistant Influenza-Infected Mice via Direct Hydrolysis of Viral RNAs

Lee

Hoang

Kim

et al. 2022

Viruses

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Emerging Oseltamivir-resistant influenza strains pose a critical public health threat due to antigenic shifts and drifts. We report an innovative strategy for controlling influenza A infections by use of a novel minibody of the 3D8 single chain variable fragment (scFv) showing intrinsic viral RNA hydrolyzing activity, cell penetration activity, and epidermal cell penetration ability. In this study, we examined 3D8 scFv’s antiviral activity in vitro on three different H1N1 influenza strains, one Oseltamivir-resistant (A/Korea/2785/2009pdm) strain, and two Oseltamivir-sensitive (A/PuertoRico/8/1934 and A/X-31) strains. Interestingly, the 3D8 scFv directly digested viral RNAs in the ribonucleoprotein complex. scFv’s reduction of influenza viral RNA including viral genomic RNA, complementary RNA, and messenger RNA during influenza A infection cycles indicated that this minibody targets all types of viral RNAs during the early, intermediate, and late stages of the virus’s life cycle. Moreover, we further addressed the antiviral effects of 3D8 scFv to investigate in vivo clinical outcomes of influenza-infected mice. Using both prophylactic and therapeutic treatments of intranasal administered 3D8 scFv, we found that Oseltamivir-resistant H1N1-infected mice showed 90% (prophylactic effects) and 40% (therapeutic effects) increased survival rates, respectively, compared to the control group. The pathological signs of influenza A in the lung tissues, and quantitative analyses of the virus proliferations supported the antiviral activity of the 3D8 single chain variable fragment. Taken together, these results demonstrate that 3D8 scFv has antiviral therapeutic potentials against a wide range of influenza A viruses via the direct viral RNA hydrolyzing activity.

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A single-chain variable fragment antibody exerts anti-nervous necrosis virus activity by irreversible binding

Huang

et al. 2022

Aquaculture

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Broad-Spectrum Antiviral Activity of 3D8, a Nucleic Acid-Hydrolyzing Single-Chain Variable Fragment (scFv), Targeting SARS-CoV-2 and Multiple Coronaviruses In Vitro

Cited by 8 publications

References 44 publications

Catalytic Antibodies: Design, Expression, and Their Applications in Medicine

Catalytic Antibodies: Design, Expression, and Their Applications in Medicine

A Therapeutically Active Minibody Exhibits an Antiviral Activity in Oseltamivir-Resistant Influenza-Infected Mice via Direct Hydrolysis of Viral RNAs

A single-chain variable fragment antibody exerts anti-nervous necrosis virus activity by irreversible binding

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