Year 23 / Nº 35 / 2021 /
El panorama de las estrategias
nanotecnológicas contra el COVID-19: productos y diagnósticos, vacunas y
tratamientos
The landscape of
nanotechnology strategies against COVID-19: products and diagnostics, vaccines
and treatments
Thyago
José Arruda Pacheco1; Franciéle de Matos da Silva1;
Danielle Galdino de Souza1,*; Victor Carlos Mello da Silva1;
Raquel Santos Faria1.
1 Institute of Biological Sciences, University of
Brasília, 70910-900, Brasília, DF, Brazil.
*E-mail: danielle.galdino@hotmail.com
Received:
21/11/2020; Approved: 09/04/2021
Resumen
El estado de
pandemia, declarado por la Organización Mundial de la Salud, el 11 de marzo de
2020, ha puesto a prueba la capacidad de adaptación y respuesta de la sociedad.
Una carrera contra el tiempo para buscar estrategias para combatir la
enfermedad del nuevo coronavirus contribuye a la unión de los científicos de
todo el mundo, incluyendo el uso de la nanotecnología. Por lo tanto, el
objetivo del estudio fue describir el panorama de las estrategias de la
nanotecnología contra COVID-19, destacando principalmente los productos y
diagnósticos, vacunas y tratamientos que son o pueden ser utilizados. Se
realizó una revisión bibliográfica de los estudios publicados entre febrero y
noviembre de 2020 en las bases de datos PubMed, Scielo y Google Scholar. Según
los índices de las distintas bases de datos, se utilizaron los términos de
búsqueda "new coronavirus 2019", "COVID-19", "severe
acute respiratory syndrome" Nanotechnology against COVID-19",
"COVID-19 Vaccines" sin ninguna restricción de idioma. El uso de
materiales de base nanométrica ha indicado un gran potencial contra la
diseminación del COVID-19, con la producción de productos, diagnósticos,
vacunas y tratamientos. Nuestros resultados demuestran que la nanotecnología
ofrece procesos, materiales y herramientas que contribuyen a aumentar la
sensibilidad, agilidad y fiabilidad del diagnóstico, además de proporcionar opciones
más eficaces para la prevención, el diagnóstico y las terapias.
Palabras clave: Coronavirus, COVID-19, Síndrome respiratorio
agudo severo, Nanotecnología, Nanomedicina.
Abstract
The pandemic state, declared by the World
Health Organization, on March 11, 2020, has tested society's adaptability and
response. A race against time to seek strategies to fight the disease of the
new coronavirus contributes to the union of scientists from all over the world,
including using nanotechnology. Thus, the objective of the study was to describe
the landscape of nanotechnology strategies against COVID-19, mainly highlighting
the products and diagnostics, vaccines and treatments that are or can be used.
A literature review was carried out in studies published from February to November
2020 in PubMed, Scielo, and Google Scholar databases. According to the indexes
of the various databases, search terms were used: “new coronavirus 2019”,
“COVID-19”, “severe acute respiratory syndrome” Nanotechnology against COVID-19”,
“COVID-19 Vaccines” without any language restrictions. The use of Nano-based
materials has indicated a great potential against dissemination of COVID-19,
with the production of products, diagnostics, vaccines and treatments. Our
results demonstrate that nanotechnology offers processes, materials and tools
that contribute to increase the sensitivity, agility and reliability of the
diagnosis, in addition to providing more effective options for prevention,
diagnosis and therapies.
Keywords: Coronavirus. COVID-19. Severe acute
respiratory syndrome. Nanotechnology. Nanomedicine.
Introduction
In December 2019, there were the first
outbreaks in China due to the novel coronavirus (SARS-COV-2). With the growing
number of cases in several countries, on March 11, 2020, the world health
organization declared the 2019 coronavirus disease pandemic (COVID-19). Since
then, scientists from different countries share the same goal: to develop
treatments, vaccines, diagnostics, and products against COVID-19.[1,2]
The different technological strategies against
COVID-19 allowed scientific and technological development also in the field of
nanotechnology, presenting a great need to better understand and explore this
novel nano-virus (60-140 nm in diameter).[3-5]
Nanotechnology provides the development of
systems under a dimension of fewer than 100 nanometers, with potential for both
diagnosis, treatment, and prevention of diseases, through nanoparticles that
have unique properties, presenting better solubility, biocompatibility,
conductivity, reduced toxicity, and multifunctionality.[6, 7]
Nanotechnology applied to the medical field is
known as nanomedicine, where nanomaterials are used for treatments, vaccines,
diagnostics, or disease prevention products.[8]
Nanomedicine, for example, is capable of being
used to improve immunogenicity with prophylactic approaches. Nanoparticles can
work basically by increasing the activation of immunity so that it protects
against disease.[9] Due to their size, 1-100 nm, nanotransporters such as
liposomes, nanoemulsions, synthetic polymeric nanoparticles, proteasomes,
nano-granules, inorganic nanomaterials, as well as biological polymeric
nanoparticles (exosome, bacteriophage) have been widely tested and used in the
prevention of infectious and non-infectious diseases, as they can be captured
by cells by endocytosis, and thus release biologically active compounds.[10,11]
Another important feature of nanotechnology in
the medical field is the ability to modify the surface and effectively co-deliver
adjuvants, which makes nanoparticles a potential candidate for commercial
vaccines. Also, nano adjuvants in vaccines protect the target antigen from
degradation and increase absorption by immunological mediators of biological
systems. This approach is malleable, having the ability to present the antigen
in a repetitive manner leading to stable immunogenic properties.[11,12] This type of nanomedicine-based approach has
already been used against SARS-CoV-1 and MERS and now with SARS-COV-2.[13]
Nanomedicine has been present in the modern
world for decades, having its first product regulated by the Federal Drug
Administration (FDA) in 1995.[14] There are many applications of nanomedicine
for different uses. Here, we highlight mainly the products and diagnostics,
vaccines and treatments that are or can be used against COVID-19.
Methods
A literature review was carried out
in studies published from February to November 2020 in PubMed, Scielo, and
Google Scholar databases. According to the indexes of the various databases,
search terms were used: “new coronavirus 2019”, “COVID-19”, “Nanotechnology
against COVID-19”, “COVID-19 Vaccines“, “severe acute respiratory syndrome”
without any language restrictions. Those who described a comparative overview
of coronavirus, treatments, vaccines, diagnostics and products nano-based against
COVID- 19 were eligible.
Results and Discussion
Products and
diagnostics
During this fight against coronavirus 2019
(COVID-19), our main line of defense is our immune system; however, people who
are immunocompromised or who have at least one underlying comorbidity are
considered to be quite vulnerable and their only line of defense is
disinfectants, facial masks, immune system stimulants and medications.[3] (Fig. 1)
Figure 1. Nanotechnology approaches in the
fight against COVID-19.
The nanotechnology field has grown a lot with
these new technological advances, and several products based on nano or
antiviral agents to block SARS-CoV-2 have been developed. [15,16] Antimicrobial
and antiviral formulations based on nanotechnology can prevent the spread of
the SARS-CoV-2 virus, and the development of highly sensitive biosensors and
detection platforms can contribute to the detection and diagnosis of COVID-19.[3]
Viral disinfectants, produced using
nano-effective antimicrobial and antiviral formulations, are suitable for
disinfecting air and surfaces and are also effective in reinforcing personal
protective equipment, such as face respirators. Metallic nanoparticles (silver,
copper, titanium dioxide nanoparticles) have been proposed as alternatives due
to their wide range of inherent antiviral activities, persistence, and ability
to be effective at much lower doses.[4]
These nanomaterials have enormous potential as
disinfectants against coronavirus, as they have intrinsic antiviral properties,
such as the generation of reactive oxygen species (ROS) and photodynamic and
photothermal capabilities. The adverse effects on human health and the
environment of metallic nanomaterials can be avoided with the use of
biodegradable (that is polymeric, lipid-based) nanomaterials.[3]
Preliminary tests showed that the silver
nanocluster coating/silica composite in disposable FFP3 face masks (3M TM) had
viricidal effects against SARS-CoV-2.[17] The NanoTechSurface developed in
Italy is a durable and self-sterilizing formula composed of titanium dioxide
and silver ions to disinfect surfaces. Graphene sheets with antibodies have the
potential to quickly detect targeted viral proteins and are also used for the
development of environmental sensors and filters, due to the low cost of
graphene materials. Functionalized graphene has demonstrated a good capacity
for viral capture that, combined with heat or light-mediated inactivation, can
be used as a disinfectant. [18] Reusable and recyclable graphene surgical masks
with excellent superhydrophobic, photothermal performances, and excellent
self-cleaning properties are commercially available. [19]
Researchers in Egypt have developed a new
device against SARS-CoV-2. This corresponds to a breathing filter mask design
based on polylactic acid (PLA), a biodegradable and transparent polymer,
cellulose acetate (CA), copper oxide nanoparticles (CuONPs), and graphene oxide
(GO). The objective is to allow the polymeric network to prevent the entry of
viral particles into the nasal cavity, while CuONPs and GO further inhibit the
potential for viral transmission by inactivating the particles trapped in the
membrane itself.[1]
Viral detection may be possible through the development
of highly sensitive and accurate nanosensors that allow early diagnosis of
COVID-19. Nanomaterials functionalized with nucleic acids or antibodies
represent the main lines of detection based on nano, through colorimetric or
antigen-binding assays, as well as light and photothermal platforms.[20]
Researchers at the Korea Institute of Basic
Sciences developed a field-effect transistor (FET) -based biosensor device to
detect SARS-CoV-2 in clinical samples. The sensor was produced by coating FET
graphene sheets with a specific antibody against the SARS-CoV-2 spike protein.
Sensor performance was determined using antigen proteins, cultured viruses, and
nasopharyngeal smear specimens from COVID-19 patients. This device has an
extraordinary ability to distinguish the SARS-CoV-2 antigen protein from those
of the MERS-CoV.[21]
Vaccines
Data from November 12nd show that there are 19
vaccines, from 212, against COVID-19, being developed and that describe in
their production method nanomedicine, such as lipid nanoparticles, liposomes,
or viral particles (DRAFT landscape of COVID-19).[21] Four of them are already
under clinical evaluation, three in phase 3 (one from Moderna / NIAID, other
from BioNTech / Fosun Pharma / Pfizer and Novavax), and the one from Imperial
College London in phase 1, the latter has not yet released its results so far (Table 1). All of these in the clinical
phase use lipid nanoparticles encapsulating RNA encoding structures of the new coronavirus.
[22] (Fig. 2)
Table 1. Description of vaccines based on
nanoparticles against COVID-19 (On November 2020).
|
Nome |
Organizações
envolvidas |
Método da
vacina |
Fase |
|
Moderna/NIAID |
National Institutes of Health
(NIH) and Moderna (United States) |
LNP (lipid nanoparticles) -encapsulated mRNA |
Fase 1 Fase 2 Fase 3 |
|
Novavax |
Novavax, Inc.
(United States) |
Full length
recombinant SARS CoV-2 glycoprotein nanoparticle vaccine adjuvanted with
Matrix M |
Fase 1/2 Fase 2b Fase 3 |
|
Ad5-nCoV |
CanSino
Biological Inc./Beijing Institute of Biotechnology (China) |
Adenovirus vector 5, containing
SARS-CoV-2 S nanoparticles |
Fase 1 Fase 2 Fase 3 |
|
BNT162 (a1,
b1, b2, c2) |
BioNTech/Fosun Pharma/Pfizer/ (United States / Germany) |
LNP-encapsulated
mRNA |
Fase 1 Fase 1/2 Fase 3 |
|
LNP-nCoVsaRNA |
Imperial
College London (England) |
LNP
encapsulated self-amplifying RNA (saRNA) |
Fase 1 |
|
Vaccine candidate |
Max-Planck-Institute
of Colloids and Interfaces (Germany) |
LNP-encapsulated
mRNA encoding the receptor
binding domain (RBD) of protein SARS-CoV-2 |
Pre-Clinical |
|
Vaccine candidate |
Bio/Sanofi Pasteur (France) |
LNP-encapsulated
mRNA |
Pre-Clinical |
|
Vaccine
candidate |
CanSino Biologics /
Precision NanoSystems (China / Canada) |
LNP-encapsulated
mRNA |
Pre-Clinical |
|
Vaccine
candidate |
Fudan
University/ Shanghai JiaoTong University/RNACure Biopharma (China) |
LNP-encapsulated mRNA encoding RBD of protein S SARS-CoV-2 |
Pre-Clinical |
|
Vaccine
candidate |
Fudan
University/ Shanghai JiaoTong University/RNACure Biopharma (China) |
LNP-encapsulated
mRNA cocktail encoding VLP |
Pre-Clinical |
|
Vaccine
candidate |
University of
Tokyo/ Daiichi-Sankyo (Japan) |
LNP-encapsulated
mRNA |
Pre-Clinical |
|
Vaccine
candidate |
BIOCAD (Russia) |
Liposome-encapsulated mRNA |
Pre-Clinical |
|
Vaccine
candidate |
Chula Vaccine
Research Center/University of Pennsylvania (United States) |
LNP-encapsulated
mRNA |
Pre-Clinical |
|
Vaccine
candidate |
National
institute of Chemistry (Slovenia) |
Plasmid DNA, nanostructured RBD |
Pre-Clinical |
|
Vaccine
candidate |
Ohio State
University / Kazakh National Agrarian University (United
States/ Kazakh) |
RBD protein
delivered in mannoseconjugated chitosan nanoparticle |
Pre-Clinical |
|
Vaccine
candidate |
Saint-Petersburg
scientific research institute of vaccines and serums (Russia) |
Recombinant
protein, nanoparticles (based on S-protein and other epitopes) |
Pre-Clinical |
|
Vaccine
candidate |
LakePharma, Inc (United
States) |
Nanoparticle vaccine |
Pre-Clinical |
|
Vaccine
candidate |
IMV Inc (Canada) |
Peptide
antigens formulated in LNP |
Pre-Clinical |
|
Vaccine
candidate |
Globe Biotech Ltd (Bangladesh) |
D614G variant LNP-encapsulated mRNA
|
Pre-Clinical |
Figure 2. Vaccines
using nanotechnology. 1) Nanometric Virus carrying “particles” of SARS-COV-2
(RNA or other subunits). 2) Nanoparticles carrying “particles” of SARS-COV-2.
These particles inside of virus or nanoparticles are responsible for
stimulating factors (like viral proteins from SARS-COV-2) that causes immune
response in several individuals.
The potential vaccine in phase 3, RNA-1273,
manufactured by ModernaTX Inc, is an mRNA-based vaccine encapsulated by lipid
nanoparticles, which is capable of encoding the Spike (S) protein of the
SARS-CoV-2 virus in the host cell. Since this RNA is encapsulated by lipid
nanoparticles, the vaccine can be injected intramuscularly into patients. So,
when injected, it takes the mRNA to host immune cells encoding the spike
protein, so these cells make copies of the protein as if the cells have been
infected by the coronavirus and then other immune cells can interact with these
spike proteins and trigger the cascade effect of the immune system, leaving the
individual protected against possible infection by the coronavirus. This
technology took just 42 days to develop and induced anti-SARS-CoV-2 immune
responses in all participants, with no limiting safety concerns identified in
the trial. [23]
The other potential vaccine with phase 3
nanotechnology is BNT162b1, manufactured by BioNTech / Fosun Pharma / Pfizer.
This is a nucleoside-modified mRNA vaccine, also formulated with lipid nanoparticles
that encode the trimerized receptor (RBD) binding domain of the SARS-CoV-2
virus spike glycoprotein. The first results of BNT162b1 were published by
Nature. Different doses were administered, with an acceptable tolerability and
safety profile, where, according to the researchers themselves, they conclude:
“The clinical findings were encouraging and strongly support the accelerated
clinical development for the rapid production of a vaccine against SARS-CoV-2
to prevent COVID- 19”.[24]
Finally, the third potential vaccine against
COVID-19 in phase 3 using nanotechnology is produced by Novovax (NVX-CoV2373).
This vaccine utilize immunogenic virus-like nanoparticles based on recombinant
expression of the S-protein. The results from phase 1-2 trial were detailed in the New England Journal
of Medicine. The NVX-CoV2373 showed good
results. being safe, and triggered immune responses that exceeded levels in
Covid-19 convalescent serum.[25]
Treatments
Several nanobiotechnological platforms were
able to combat human viruses, and preclinical studies, such as herpes,
hepatitis B, HIV, in addition to some respiratory viruses.[26,27] These
platforms can be used to develop therapies and diagnoses against SARS-CoV-2 or
other future pandemics.[13,28,29]
When analyzing the panorama of the therapeutic
development of COVID-19 with other diseases, we can see that, in both cases,
the most important thing is to align the correct drug with the most promising
nanocarrier. [30] Thus, we can infer that the challenges for the development of
therapies against COVID-19, as well as for other viral diseases or even cancer,
for example, are very similar.[31-32]
However, in general aspects, the encounter of
the virus with the susceptible host is what makes viral infection possible. We
can divide four very important points of the relationship between viruses and
host cells for the maintenance of the infectious process. First - the
adsorption and penetration of the viral agent in the host; second -
transcription, translation (synthesis) and maturation of the viable progeny;
third - the release of the host's progeny; and fourth - the resistance of the
viral agent to the adversities of the environment.[33]
According to that, we can also observe that
therapeutic drugs based on NP can inhibit the effects of viral infections in
three main ways (I) blocking receptor binding and entering the cell, (II)
inhibiting viral infection, and (III) viral inactivation.
(I) Blocking the binding to the receptor and
entering the cell, as shown in the work by Huang et al.[34] (2019), where the
AuNRs nanoparticle blocked the entry of the MERS virus.[26] AgNPs showed
efficient antiviral activity against RSV (herpes simplex virus) infection by
directly inactivating the virus before entering host cells.[35] Silica
nanoparticles (SiNPs) can act as efficient eliminators of the human
immunodeficiency virus (HIV) and the respiratory syncytial virus (RSV).[36]
(II) The inhibition of viral infection, as
shown in the study by Lin and coauthors (2017), Se @ ZNV (selenium
nanoparticles with the antiviral zanamivir) revealed good biological activity
to contain the proliferation of the influenza virus H1N1.[37] According to
Silva and coauthors[38], (2016), SiO NPs were able to inhibit HIV infection,
showing that the use of these functionalized silica particles presented a
promising approach for the control of HIV infection and viral control.[38]
(III) Viral inactivation, as presented in the
study by Ghaffari and coauthors[30] (2019), the PEGylated ZnO-NPs nanoparticles
had an antiviral activity with inhibitory properties against the H1N1 influenza
virus.[39] Kong and coauthors[40] (2019) observed that nanodisks inhibited the
infection of the influenza virus H1N1, even suggesting nanodisks as therapeutic
agents against enveloped viruses.[41] (Fig. 3)
Figure 3. Nanoparticles inhibiting the effects
of viral infections in three main ways. (I) blocking receptor binding and
entering the cell, (II) inhibiting proliferation, and (III) viral inactivation.
Despite the treatment options currently
proposed, the number of serious cases and deaths of patients infected with
SARS-CoV-2 is still high. Much of the side effects of antivirals are caused by
their accumulation in off-target organs. Nanoparticles can optimize drug
delivery to target infection sites and with controlled release properties. [42]
Therefore, we must also focus on alternative approaches, such as
nanotechnology, to achieve an effective treatment for this disease and to
minimize the side effects of the compounds.
Conclusion
There are several options for products,
treatments, and vaccines nano-based against COVID-19. The great hope is placed
on vaccines and three of them, in phase 3, use nanotechnology. Nanomedicine has
already demonstrated its ability to protect, diagnose, and treat other viral
diseases or infections; therefore, it may also have a great capacity to fight
COVID-19. One of the biggest challenges is ensuring the safe use of these
nanomaterials for the entire world population.
Acknowledgements
The authors gratefully acknowledge financial
support from: the Brazilian National Council for Technological and Scientific
Development (CNPq), Coordinating Agency for Advanced Training of Graduate Personnel (CAPES), Foundation for Research
Support of the Federal
District (FAPDF)
an the Dean of Research and Post-Graduation of the University of Brasília
(DPP-UnB).
References
1. Ahmed M K, Afifi M, Uskokovic V. Protecting
healthcare workers during COVID-19 pandemic with nanotechnology: A protocol for
a new device from Egypt. Journal of
Infection and Public Health. 2020, 13(9):1243–1246.
2. Pacheco TJA, Silva FM, Souza DG, Silva VCM, Faria, RS.
Coronavirus disease 2019 (COVID-19): updated evidence of comparative overview,
diagnosis and treatments. Revista Cereus. 2020, 12:228-243.
3. Talebian S, Wallace GG, Schroeder,
Francesco S, João C. Nanotechnology-based disinfectants and sensors for
SARS-CoV-2. Nature Nanotechnology.
2020, 15(8):618–621.
4. Sportelli MC et al. Can Nanotechnology and Materials Science Help the
Fight against SARS-CoV-2? Nanomaterials.
2020, 10(802).
5. Tabish T A, Hamblin M R. Multivalent
nanomedicines to treat COVID-19: A slow train coming. Nano Today. 2020, 35(1748– 0132):4.
6. Campos E V R et al. How can nanotechnology
help to combat COVID-19? Opportunities and urgent need. Journal of Nanobiotechnology. 2020, 18(1):1–23.
7. Vazquez-Munoz R, Lopez-Ribot J L.
Nanotechnology as an Alternative to Reduce the Spread of COVID-19. Challenges. 2020, 11(2):15.
8. Choi Y H, Han H K. Nanomedicines: current status
and future perspectives in aspect of drug delivery and pharmacokinetics.
Journal of Pharmaceutical Investigation. 2018, 48(1): 43–60.
9. Yadav H K S. et al. Nanovaccines formulation
and applications-a review. Journal of
Drug Delivery Science and Technology. 2018, 44:380–387.
10. Zaman, M.; Good, M. F.; Toth, I.
Nanovaccines and their mode of action. Methods.
2013, 60(3): 226–231.
11. Zhao L. et al. Nanoparticle vaccines. Vaccine. 2014, 32:327–337.
12. Vicente S. et al. From single-dose vaccine
delivery systems to nanovaccines. Journal of Drug Delivery Science and
Technology. 2010, 20(4):267–276.
13. Chan, W. C. W. Nano Research for COVID-19. ACS Nano, v. 14, p. 3719–3720, 2020.
14. Fluhmann B. et al. Nanomedicines: The magic bullets reaching their target? European Journal of Pharmaceutical Sciences.
2019, 128:73–80.
15. Itani R, Tobaiqy M, Faraj A Al. Optimizing
use of theranostic nanoparticles as a life-saving strategy for treating
COVID-19 patients. Theranostics. 2020,
10(13):5932–5942.
16. Faraj Z. O. A.
Covid-19 Pandemic: Lessons to Learn from China. Oman Medical Journal. 2020,
35(4):1–2.
17. Balagna C, Perero S, Percivalle E,
Nepita EV, Ferraris M. Virucidal
effect against coronavirus SARS-CoV-2 of a silver nanocluster/ silica composite
sputtered coating. Open Ceramics. 2020, 1(2666–5395):3.
18. Palmieri V, Papi M. Can graphene take part
in the fight against COVID-19? Nano Today. 2020, 33(1748– 0132):1–4.
19. Zhong H. et al. Reusable and Recyclable
Graphene Masks with Outstanding Superhydrophobic and Photothermal Performances.
ACS Nano. 2020, 14(5):6213–6221.
20. Li Z. et al. Development and clinical
application of a rapid IgM-IgG combined antibody test for SARS-CoV-2 infection
diagnosis. Journal of Medical Virology. 2020, 92(9):1518–1524.
21. Seo G. et al. Rapid Detection of COVID-19
Causative Virus (SARS-CoV-2) in Human Nasopharyngeal Swab Specimens Using
Field-Effect Transistor-Based Biosensor. ACS nano. 2020, 14(4):5135–5142.
22. DRAFT landscape of COVID-19 candidate
vaccines. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidatevaccines.
Accessed: 2020 oct. 19.
23. Jackson L. A. et al. An mRNA Vaccine
against SARS-CoV-2 — Preliminary Report. New England Journal of Medicine, 2020.
24. Mulligan M J. et al. Phase 1/2 study of
COVID-19 RNA vaccine BNT162b1 in adults. Nature, 2020.
25. Keech,
Cheryl et al. Phase 1–2 trial of a SARS-CoV-2 recombinant spike protein
nanoparticle vaccine. New England
Journal of Medicine, 2020.
26. Jackman, J. A.; Lee, J.; Cho, N. J.
Nanomedicine for Infectious Disease Applications: Innovation towards
Broad-Spectrum Treatment of Viral Infections. Nano. Micro Small. 2016,
12(9):1133–1139.
27. Patel S. et al. Nanoparticles as a Platform
for Antimicrobial Drug Delivery. Advances
in Pharmacology and Pharmacy. 2017, 5(3):31–43.
28. Amanat, F.; Krammer, F. SARS-CoV-2
Vaccines: Status Report. Immunity.
2020, 52:583–589.
29. Weiss C. et al. Toward
Nanotechnology-Enabled Approaches against the COVID-19 Pandemic. ACS Nano. 2020, 14(6):6383–6406.
30. Chauhan G. et al. Nanotechnology for
COVID-19: Therapeutics and Vaccine Research. ACS Nano. 2020, 14(7):7760–7782.
31. Lammers T. et al. Dexamethasone
nanomedicines for COVID-19. Nature
Nanotechnology. 2020, 15(8):618–621.
32. Meel, R. Van Deer et al. Smart cancer
nanomedicine: Strategic directions to improve translation and exploitation. HHS
Public Access. 2019, 14(11):1007–1017.
33. Kostarelos, K. Nanoscale nights of COVID-19. Nature Nanotechnology. 2020, 15:343–344.
34. Oliveira, M.
B. S. C. D., & Ribeiro, F. C. Virologia. EPSJV. 2009.
35. Huang X. et al. Novel Gold Nanorod-Based
HR1 Peptide Inhibitor for Middle East Respiratory Syndrome Coronavirus. ACS
Applied Materials and Interfaces. 2019, 11(22): 19799–19807.
36. Yang, X. Xi; Mei, C.; Huang, C. Z. Curcumin
modified silver nanoparticles for higly efficient inhibition of respiratory
syncytial virus infiction. Nanoscale. 2016, 8(3040):1–9.
37. Osminkina L. A. et al. Porous silicon
nanoparticles as scavengers of hazardous viruses. Journal of Nanoparticle
Research. 2014, 16(6).
38. Lin Z. et al. Inhibition of H1N1 influenza
virus by selenium nanoparticles loaded with zanamivir through p38 and JNK
signaling pathways. RSC Advances. 2017, 7(56):35290–35296.
39. Silva J M S. et al. Viral Inhibition
Mechanism Mediated by Surface-Modified Silica Nanoparticles. ACS Applied
Materials and Interfaces, 2016, 8(26):16564–16572.
40. Ghaffari H. et al. Inhibition of H1N1
influenza virus infection by zinc oxide nanoparticles: Another emerging
application of nanomedicine. Journal of Biomedical Science. 2019, 26(1):1–10.
41. Kong B. et al. Virucidal nano-perforator of
viral membrane trapping viral RNAs in the endosome. Nature Communications.
2019, 10(1).
42. Chhikara B S. Current trends in
nanomedicine and nanobiotechnology research. Journal of Materials NanoScience.
2017, 4(1):19-24.