A Detailed Overview of Immune Escape, Antibody Escape, Partial Vaccine Escape of SARS-CoV-2 and Their Emerging Variants With Escape Mutations

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 9, 2022

The infective SARS-CoV-2 is more prone to immune escape. Presently, the significant variants of are emerging in due course time with substantial mutations, having escape property. Simultaneously, vaccination drive against this virus progress worldwide. However, vaccine evasion has been noted by some newly variants. Our review provides an overview variants' and ability. We have illustrated a broad view related viral evolution, variants, Subsequently, different approaches discussed. Different innate strategies adopted discussed like, IFN-I production dysregulation, cytokines escape, associated dendritic cell function macrophages, natural killer cells neutrophils PRRs evasion, NLRP3 inflammasome evasion. Simultaneously we mutations such as RBD region (N439K, L452R, E484K, N501Y, K444R) other parts (D614G, P681R) S-glycoprotein. Mutations locations NSP1, NSP3, NSP6, ORF3, ORF8 also Finally, partial (BioNTech/Pfizer mRNA/Oxford-AstraZeneca/BBIBP-CorV/ZF2001/Moderna mRNA/Johnson & Johnson vaccine) This will help gain in-depth knowledge antibody ability assist controlling current pandemic prepare for next.

Language: Английский

---

Nanobody—A versatile tool for cancer diagnosis and therapeutics

Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology, Journal Year: 2021, Volume and Issue: 13(4)

Published: Jan. 20, 2021

In spite of the successful use monoclonal antibodies (mAbs) in clinic for tumor treatment, their applications are still hampered therapeutic development due to limitations, such as penetration and high cost manufacture. Nanobody, a single domain antibody that holds strong antigen targeting binding capacity, has demonstrated various advantages relative antibody. Nanobody is considered next-generation antibody-derived tool related recognition modulation. A number nanobodies have been developed evaluated different stages clinical trials cancer treatment. Here we summarized current progress nanobody diagnosis therapeutics, particularly on conjugation with functional moieties. The diagnostic agents, radionuclide optical tracers, can achieve specific imaging. nanobody-drug conjugates enhance efficacy anti-tumor drugs reduce adverse effects. decoration nanodrug delivery systems further improve drug tumors. This article categorized under: Therapeutic Approaches Drug Discovery > Nanomedicine Oncologic Disease.

Language: Английский

---

Epigallocatechin-3-gallate, an active ingredient of Traditional Chinese Medicines, inhibits the 3CLpro activity of SARS-CoV-2

International Journal of Biological Macromolecules, Journal Year: 2021, Volume and Issue: 176, P. 1 - 12

Published: Feb. 4, 2021

Language: Английский

---

Nanotechnology-based strategies against SARS-CoV-2 variants

Nature Nanotechnology, Journal Year: 2022, Volume and Issue: 17(10), P. 1027 - 1037

Published: Aug. 18, 2022

Language: Английский

---

Molnupiravir and Its Antiviral Activity Against COVID-19

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 4, 2022

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome 2 (SARS-CoV-2) constitutes a major worldwide public health threat and economic burden. is still ongoing the SARS-CoV-2 variants are emerging constantly, resulting in an urgent demand for new drugs to treat this disease. Molnupiravir, biological prodrug of NHC (β-D-N(4)-hydroxycytidine), novel nucleoside analogue with broad-spectrum antiviral activity against SARS-CoV, SARS-CoV-2, Middle East (MERS-CoV), influenza virus, syncytial virus (RSV), bovine viral diarrhea (BVDV), hepatitis C (HCV) Ebola (EBOV). Molnupiravir showed potent therapeutic prophylactic multiple coronaviruses including MERS-CoV animal models. In clinical trials, molnupiravir beneficial effects mild moderate COVID-19 patients favorable safety profile. oral bioavailability highlight its potential utility as candidate COVID-19. This review presents research progress starting discovery synthesis, effects, mechanism. addition, preclinical studies, resistance, safety, drug tolerability also summarized discussed, aiming expand our knowledge on better deal epidemic.

Language: Английский

---

Multivalent designed proteins neutralize SARS-CoV-2 variants of concern and confer protection against infection in mice

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(646)

Published: April 12, 2022

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise and prolong the disease 2019 (COVID-19) pandemic. Here, we used a cell-free expression workflow rapidly screen optimize constructs containing multiple computationally designed miniprotein inhibitors SARS-CoV-2. We found broadest efficacy was achieved with homotrimeric version 75-residue angiotensin-converting enzyme (ACE2) mimic AHB2 (TRI2-2) geometrically match trimeric spike architecture. Consistent design model, in cryo-electron microscopy structure TRI2-2 forms tripod at apex protein that engaged all three receptor binding domains simultaneously. neutralized Omicron (B.1.1.529), Delta (B.1.617.2), other tested greater potency than monoclonal antibodies clinically for treatment COVID-19. also conferred prophylactic therapeutic protection against SARS-CoV-2 challenge when administered intranasally mice. Designed mimics arrayed pathogen sites could be widely applicable antiviral strategy advantages over resistance viral escape antigenic drift, native traps lower chances autoimmune responses.

Language: Английский

---

A bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 10, 2022

Antibodies binding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike have therapeutic promise, but emerging variants show potential for virus escape. This emphasizes need molecules with distinct and novel neutralization mechanisms. Here we describe isolation of a nanobody that interacts simultaneously two RBDs from different trimers SARS-CoV-2, rapidly inducing formation trimer-dimers leading loss their ability attach host cell receptor, ACE2. We this potently neutralizes including beta delta variants, cross-neutralizes SARS-CoV. Furthermore, demonstrate against SARS-CoV-2 variant in human ACE2 transgenic mouse model. naturally elicited bispecific monomeric establishes an uncommon strategy potent inactivation viral antigens represents promising antiviral variants.

Language: Английский

---

The Dawn of a New Era: Targeting the “Undruggables” with Antibody-Based Therapeutics

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(12), P. 7782 - 7853

Published: May 15, 2023

The high selectivity and affinity of antibodies toward their antigens have made them a highly valuable tool in disease therapy, diagnosis, basic research. A plethora chemical genetic approaches been devised to make accessible more "undruggable" targets equipped with new functions illustrating or regulating biological processes precisely. In this Review, addition introducing how naked various antibody conjugates (such as antibody-drug conjugates, antibody-oligonucleotide antibody-enzyme etc.) work therapeutic applications, special attention has paid chemistry tools helped optimize the outcome (i.e., enhanced efficacy reduced side effects) facilitate multifunctionalization antibodies, focus on emerging fields such targeted protein degradation, real-time live-cell imaging, catalytic labeling decaging spatiotemporal control well engagement inside cells. With advances modern biotechnology, well-designed derivatives via size miniaturization together efficient delivery systems emerged, which gradually improved our understanding important paved way pursue novel for potential treatments diseases.

Language: Английский

---

Nanobodies: Robust miniprotein binders in biomedicine

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 195, P. 114726 - 114726

Published: Feb. 7, 2023

Language: Английский

---

Assessing antibody and nanobody nativeness for hit selection and humanization with AbNatiV

Nature Machine Intelligence, Journal Year: 2024, Volume and Issue: 6(1), P. 74 - 91

Published: Jan. 15, 2024

Abstract Monoclonal antibodies have emerged as key therapeutics. In particular, nanobodies, small, single-domain that are naturally expressed in camelids, rapidly gaining momentum following the approval of first nanobody drug 2019. Nonetheless, development these biologics therapeutics remains a challenge. Despite availability established vitro directed-evolution technologies relatively fast and cheap to deploy, gold standard for generating therapeutic discovery from animal immunization or patients. Immune-system-derived tend favourable properties vivo, including long half-life, low reactivity with self-antigens toxicity. Here we present AbNatiV, deep learning tool assessing nativeness is, their likelihood belonging distribution immune-system-derived human camelid nanobodies. AbNatiV is multipurpose accurately predicts Fv sequences any source, synthetic libraries computational design. It provides an interpretable score immunogenicity, residue-level profile can guide engineering nanobodies indistinguishable ones. We further introduce automated humanization pipeline, which applied two Laboratory experiments show AbNatiV-humanized retain binding stability at par better than wild type, unlike humanized using conventional structural residue-frequency analysis. make available downloadable software webserver.

Language: Английский

---