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 10 publications

(6 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 1 ) This type of study has increased worldwide, and many interesting reports have been published in the USA, 14 , 40 – 43 ) Europe, 44 – 51 ) and Africa/Asia. 52 – 54 ) The catalytic antibody has potential in future applications due to its high catalytic activity to cleave the peptide bond of targeting peptides, as well as proteins. In addition, it can cleave DNA (or RNA), which can lead to the suppression of viral infection.…”

Section: Conclusion Opinions and Prospectsmentioning

confidence: 99%

Direct conversion of a general antibody to its catalytic antibody and corresponding applications —Importance and role of Pro95 in CDR-3—

Hifumi

Taguchi

Nonaka

et al. 2023

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

View full text Add to dashboard Cite

Catalytic antibodies possess unique features capable of both recognizing and enzymatically degrading antigens. Therefore, they are more beneficial than monoclonal antibodies (mAbs). Catalytic antibodies exhibit the ability to degrade peptides, antigenic proteins, DNA, and physiologically active molecules. However, they have a significant drawback in terms of their production. The production of a desired catalytic antibody has extensive costs, in terms of time and effort. We herein describe an evolutionary method to produce a desired catalytic antibody via conversion of a general antibody by the deletion of Pro95, which resides in complementarity-determining region-3. As over thousands of mAbs have been produced since 1975, using the novel technology discussed herein, the catalytic feature cleaving the antigen can be conferred to the mAb. In this review article, we discussed in detail not only the role of Pro95 but also the unique features of the converted catalytic antibodies. This technique will accelerate research on therapeutic application of catalytic antibodies.

show abstract

Section: Conclusion Opinions and Prospectsmentioning

confidence: 99%

Direct conversion of a general antibody to its catalytic antibody and corresponding applications —Importance and role of Pro95 in CDR-3—

Hifumi

Taguchi

Nonaka

et al. 2023

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

View full text Add to dashboard Cite

show abstract

“…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%

See 1 more Smart Citation

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

Zhao

Chen

et al. 2022

Appl Biochem Biotechnol

View full text Add to dashboard Cite

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.

show abstract

“…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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

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 10 publications

References 45 publications

Direct conversion of a general antibody to its catalytic antibody and corresponding applications —Importance and role of Pro95 in CDR-3—

Direct conversion of a general antibody to its catalytic antibody and corresponding applications —Importance and role of Pro95 in CDR-3—

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

Contact Info

Product

Resources

About