Nanobodies as powerful pulmonary targeted biotherapeutics against SARS-CoV-2, pharmaceutical point of view

Abstract

Background Since December 2019, the newly emerged SARS-CoV-2 virus continues to infect humans and many people died from severe Covid-19 during the last 2 years worldwide. Different approaches are being used for treatment of this infection and its consequences, but limited results have been achieved and new therapeutics are still needed. One of the most interesting biotherapeutics in this era are Nanobodies which have shown very promising results in recent researches. Scope of review Here, we have reviewed the potentials of Nanobodies in Covid-19 treatment. We have also discussed the properties of these biotherapeutics that make them very suitable for pulmonary drug delivery, which seems to be very important route of administration in this disease. Major conclusion Nanobodies with their special biological and biophysical characteristics and their resistance against harsh manufacturing condition, can be considered as promising, targeted biotherapeutics which can be administered by pulmonary delivery pharmaceutical systems against Covid-19. General significance Covid-19 has become a global problem during the last two years and with emerging mutant strains, prophylactic and therapeutic approaches are still highly needed. Nanobodies with their specific properties can be considered as valuable and promising candidates in Covid-19 therapy.

Bovine-derived antibodies and camelid-derived nanobodies as biotherapeutic weapons against SARS-CoV-2 and its variants: A review article

“…The therapeutic potential of camel nanobodies against COVID-19 has been recently emphasized and proposed to be useful as Dromedary camels could act as a natural source of SARS-CoV-2 neutralizing nanobodies [ 46 , 50 , 54 , 79 ] ( Table 5 ) . Nanobodies are one of the most intriguing biotherapeutics in this era, with promising outcomes in recent studies [ 79 ]. Several SARS-CoV-2 epitopes were found highly immunogenic in humans, and some epitopes can be wholly targeted by camel antibodies.…”

“…They are, therefore, inaccessible to conventional antibodies and thus penetrate tissues deeply [ [84] , [85] , [86] ]. For example, when nanobodies are used as an inhalant, high pulmonary drug concentrations are achieved, but systemic drug concentrations are kept low, and systemic adverse effects are kept to a minimum [ 50 , 79 ]. Nanobodies can be used in different formats, and currently, nearly fifteen Nanobodies developed against SARS-CoV-2 during the Covid-19 pandemic [ 79 ], mostly targeted receptor-binding domain (RBD) [ 79 ].…”

“…For example, when nanobodies are used as an inhalant, high pulmonary drug concentrations are achieved, but systemic drug concentrations are kept low, and systemic adverse effects are kept to a minimum [ 50 , 79 ]. Nanobodies can be used in different formats, and currently, nearly fifteen Nanobodies developed against SARS-CoV-2 during the Covid-19 pandemic [ 79 ], mostly targeted receptor-binding domain (RBD) [ 79 ]. Among wellsprings of these nanobodies are camels immunized with RBD, llama, and/or Alpaca immunized with spike protein and/or RBD, and Naïve library from llamas and/or alpacas [ 79 ].…”

“…Nanobodies can be used in different formats, and currently, nearly fifteen Nanobodies developed against SARS-CoV-2 during the Covid-19 pandemic [ 79 ], mostly targeted receptor-binding domain (RBD) [ 79 ]. Among wellsprings of these nanobodies are camels immunized with RBD, llama, and/or Alpaca immunized with spike protein and/or RBD, and Naïve library from llamas and/or alpacas [ 79 ]. Nanobodies are efficiently produced in various prokaryotic and eukaryotic hosts, including bacteria ( E. coli ), yeast ( Pichia pastoris ), and mammalian cells [ 79 ].…”

“…Among wellsprings of these nanobodies are camels immunized with RBD, llama, and/or Alpaca immunized with spike protein and/or RBD, and Naïve library from llamas and/or alpacas [ 79 ]. Nanobodies are efficiently produced in various prokaryotic and eukaryotic hosts, including bacteria ( E. coli ), yeast ( Pichia pastoris ), and mammalian cells [ 79 ]. Multivalent Nbs can be further classified into bivalent (two identical Nbs), biparatropic (two different Nbs), or trivalent (three identical Nbs) [ 14 ].…”