Biopharmaceuticals Laboratory, Instituto Butantan, São Paulo, Brazil.
University of São Paulo, Sao Paulo, Brazil.
Front Immunol. 2022 Jul 11;13:871874. doi: 10.3389/fimmu.2022.871874. eCollection 2022.
The COVID-19 pandemic caused by the severe acute syndrome virus 2 (SARS-CoV-2) has been around since November 2019. As of early June 2022, more than 527 million cases were diagnosed, with more than 6.0 million deaths due to this disease. Coronaviruses accumulate mutations and generate greater diversity through recombination when variants with different mutations infect the same host. Consequently, this virus is predisposed to constant and diverse mutations. The SARS-CoV-2 variants of concern/interest (VOCs/VOIs) such as Alpha (B.1.1.7), Beta (B.1.351), Gamma (B.1.1.28/P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) have quickly spread across the world. These VOCs and VOIs have accumulated mutations within the spike protein receptor-binding domain (RBD) which interacts with the angiotensin-2 converting enzyme (ACE-2) receptor, increasing cell entry and infection. The RBD region is the main target for neutralizing antibodies; however, other notable mutations have been reported to enhance COVID-19 infectivity and lethality. Considering the urgent need for alternative therapies against this virus, an anti-SARS-CoV-2 equine immunoglobulin F(ab'), called ECIG, was developed by the Butantan Institute using the whole gamma-irradiated SARS-CoV-2 virus. Surface plasmon resonance experiments revealed that ECIG binds to wild-type and mutated RBD, S1+S2 domains, and nucleocapsid proteins of known VOCs, including Alpha, Gamma, Beta, Delta, Delta Plus, and Omicron. Additionally, it was observed that ECIG attenuates the binding of RBD (wild-type, Beta, and Omicron) to human ACE-2, suggesting that it could prevent viral entry into the host cell. Furthermore, the ability to concomitantly bind to the wild-type and mutated nucleocapsid protein likely enhances its neutralizing activity of SARS-CoV-2. We postulate that ECIG benefits COVID-19 patients by reducing the infectivity of the original virus and existing variants and may be effective against future ones. Impacting the course of the disease, mainly in the more vulnerable, reduces infection time and limits the appearance of new variants by new recombination.
由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起的 COVID-19 大流行始于 2019 年 11 月。截至 2022 年 6 月初，已诊断出超过 5.27 亿例病例，并有超过 600 万人因该病死亡。当具有不同突变的变体感染同一宿主时，冠状病毒通过重组积累突变并产生更大的多样性。因此，这种病毒容易发生持续和多样的突变。SARS-CoV-2 的关切/感兴趣变体（VOCs/VOIs），如 Alpha（B.1.1.7）、Beta（B.1.351）、Gamma（B.1.1.28/P.1）、Delta（B.1.617.2）和 Omicron（B.1.1.529），已迅速在全球范围内传播。这些 VOCs 和 VOIs 在与血管紧张素转换酶（ACE-2）受体相互作用的刺突蛋白受体结合域（RBD）内积累了突变，增加了细胞进入和感染。RBD 区域是中和抗体的主要靶标；然而，已经报道了其他显著的突变可以增强 COVID-19 的感染力和致死率。考虑到对抗这种病毒的替代疗法的迫切需求，布坦坦研究所使用全伽马辐照的 SARS-CoV-2 病毒开发了一种针对 SARS-CoV-2 的马免疫球蛋白 F(ab')，称为 ECIG。表面等离子体共振实验表明，ECIG 结合野生型和突变的 RBD、S1+S2 结构域以及已知 VOC 的核衣壳蛋白，包括 Alpha、Gamma、Beta、Delta、Delta Plus 和 Omicron。此外，观察到 ECIG 减弱了 RBD（野生型、Beta 和 Omicron）与人类 ACE-2 的结合，表明它可以阻止病毒进入宿主细胞。此外，同时结合野生型和突变的核衣壳蛋白的能力可能增强了其对 SARS-CoV-2 的中和活性。我们假设 ECIG 通过降低原始病毒和现有变体的感染力来使 COVID-19 患者受益，并且可能对未来的变体有效。通过减少感染时间和限制新重组产生的新变体，从而影响疾病进程，主要是在更脆弱的人群中。
