The coronavirus disease 2019 (COVID‐19) pandemic has become a serious burden on global public health. Although therapeutic drugs against COVID‐19 have been used in many countries, their efficacy is still limited. We here reported nanobody (Nb) phage display libraries derived from four camels immunized with the SARS‐CoV‐2 spike receptor‐binding domain (RBD), from which 381 Nbs were identified to recognize SARS‐CoV‐2‐RBD. Furthermore, seven Nbs were shown to block interaction of human angiotensin‐converting enzyme 2 (ACE2) with SARS‐CoV‐2‐RBD variants and two Nbs blocked the interaction of human ACE2 with bat‐SL‐CoV‐WIV1‐RBD and SARS‐CoV‐1‐RBD. Among these candidates, Nb11‐59 exhibited the highest activity against authentic SARS‐CoV‐2 with 50% neutralizing dose (ND₅₀) of 0.55 μg/ml. Nb11‐59 can be produced on large scale in Pichia pastoris, with 20 g/L titer and 99.36% purity. It also showed good stability profile, and nebulization did not impact its stability. Overall, Nb11‐59 might be a promising prophylactic and therapeutic molecule against COVID‐19, especially through inhalation delivery.

Therapeutic monoclonal antibodies and Fc-fusion proteins are successfully used in treatment of various diseases mainly including cancer, immune disease, and viral infection, which belong to the Fc-based therapeutics. In recent years, engineered Fc-derived antibody domains have also shown potential for Fc-based therapeutics. To increase the druggability of Fc-based therapeutic candidates, many efforts have been made in optimizing physicochemical properties and functions mediated by Fc fragment. The desired result is that we can simultaneously obtain Fc variants with increased physicochemical properties in vitro and capacity of mediating appropriate functions in vivo. However, changes of physicochemical properties of Fc may result in alternation of Fc-mediated functions and vice versa, which leads to undesired outcomes for further development of Fc-based therapeutics. Therefore, whether modified Fc fragments are suitable for achievement of expected clinical results or not needs to be seriously considered. Now, this question comes to be noticed and should be figured out to make better translation from the results of laboratory into clinical applications. In this review, we summarize different strategies on engineering physicochemical properties of Fc, and preliminarily elucidate the relationships between modified Fc in vitro and the subsequent therapeutic influence in vivo.

The 2022 mpox outbreak led the World Health Organization (WHO) to declare it a public health emergency of international concern (PHEIC). There is a need to develop more effective and safer mpox virus (MPXV)-specific vaccines in response to the mpox epidemic. The mRNA vaccine is a promising platform to protect against MPXV infection. In this study, we construct two bivalent MPXV mRNA vaccines, designated LBA (B6R-A29L) and LAM (A35R-M1R), and a quadrivalent mRNA vaccine, LBAAM (B6R-A35R-A29L-M1R). The immunogenicity and protective efficacy of these vaccines alone or in combination were evaluated in a lethal mouse model. All mRNA vaccine candidates could elicit potential antigen-specific humoral and cellular immune responses and provide protection against vaccinia virus (VACV) infection. The protective effect of the combination of two bivalent mRNA vaccines and the quadrivalent vaccine was superior to that of the individual bivalent mRNA vaccine. Our study provides valuable insights for the development of more efficient and safer mRNA vaccines against mpox.

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012, and circulated worldwide with high mortality. The continual outbreaks of MERS-CoV highlight the importance of developing antiviral therapeutics. Here, we rationally designed a novel fusion inhibitor named MERS-five-helix bundle (MERS-5HB) derived from the six-helix bundle (MERS-6HB) which was formed by the process of membrane fusion. MERS-5HB consists of three copies of heptad repeat 1 (HR1) and two copies of heptad repeat 2 (HR2) while MERS-6HB includes three copies each of HR1 and HR2. As it lacks one HR2, MERS-5HB was expected to interact with viral HR2 to interrupt the fusion step. What we found was that MERS-5HB could bind to HR2P, a peptide derived from HR2, with a strong affinity value (K_D) of up to 0.24 nM. Subsequent assays indicated that MERS-5HB could inhibit pseudotyped MERS-CoV entry effectively with 50% inhibitory concentration (IC₅₀) of about 1 μM. In addition, MERS-5HB significantly inhibited spike (S) glycoprotein-mediated syncytial formation in a dose-dependent manner. Further biophysical characterization showed that MERS-5HB was a thermo-stable α-helical secondary structure. The inhibitory potency of MERS-5HB may provide an attractive basis for identification of a novel inhibitor against MERS-CoV, as a potential antiviral agent.