Piperine, a compound found in black pepper, has been shown in computational studies to have strong binding affinity for SARS-CoV-2 proteins and may inhibit the virus from entering cells. Piperine has anti-inflammatory and antioxidant effects that could help combat COVID-19. Studies have also found piperine increases the bioavailability of other compounds like curcumin and may help support immune function. Computational docking simulations indicate piperine has potential as an antiviral agent against COVID-19.

1. Piper nigrum, fam. Piperaceae
BIBER

2. BIBER
Istorijat
• Za razliku od soli, koja se može naći praktično bilo gde u svetu, crni biber se
nalazi samo u Kerali, provinciji u jugozapadnoj Indiji.
• Pominjanje bibera se pojavljuje u grčkim i rimskim tekstovima, što ukazuje na
drevnu trgovinu između Indije i Zapada.
• Za biber su znali i drevni Egipćani, iako nije tačno utvrđeno kako je ovaj začin
dopreman u Egipat.
• Još od 1000 godina pre nove ere, trgovci iz južne Arabije su kontrolisali trgovinu
začina i bibera, imajući veliki monopol nad sve profitabilnijim poslovanjem. Kako
bi zaštitili svoje vredne rute, trgovci su izmišljali priče o teškoćama koje su
preživljavali kako bi nabavili začine, tako da niko nije želeo da putuje svetom i ide
u nabavku začina, rizikujući da ga “napadne zmaj koji čuva biber”.
• https://www.ediskont.rs/sr/clanak/mala-istorija-bibera

4. BIBER "King of spices"
" Black gold"
History Researchers pointed out that black pepper marked the history of
humankind that the mummy of Ramesses II of ancient Egypt, dating back at least
as early as 13th century BCE, contained black pepper. Moreover, Ahmad in his
book, advanced that nearly 3000 years before the birth of Christ, both
Babylonians and Assyrians were trading in spices, primarily black pepper, with
the people of the Malabar coast in the state of Kerala on the Indian subcontinent/
Црни бибер који је пореклом из јужне и југоисточне Азије, као зачин у индијској
кухињи почео је да се користи још пре 4 миленијума (у XX веку пре нове ере). За
бибер су знали и древни Египћани, иако није тачно утврђено на који начин је овај
зачин допреман у Египат. Зрна црног бибера пронађена су у носницама мумије
фараона Рамзеса II (преминуо 1213. пре нове ере), али није јасно да ли је бибер
кориштен као средство приликом мумифицирања, или је имао религијску
ритуалну вредност.

5. BIBER"King of spices"
" Black gold"
U srednjm veku, trgovački putevi još uvek su čvrsto kontrolisali muslimanski trgovci,
dok su italijanski gradovi poput Venecije i Đenove držali monopol na brodskim
linijama kada je začin došao do Mediterana.
Biber je bilo teško isporučivati – jer se Put svile, najpoznatiji trgovački put, širio na
preko 4.000 milja - ali biber je bio poželjan začin na koji su italijanski trgovci u suštini
mogli da postave svoje cene.
To je dovelo do toga da biber dobije status luksuznog artikla u srednjovekovnoj Evropi
a njime su se čak plaćali i porezi. Koliko je biber u to vreme bio skup najbolje se
ogleda u holandskoj reči „peperduur” („skup kao biber”) kojom su se označavale
skupe i luksuzne stvari, a verovatno se otuda i kod nas kaže „papreno skup”.

6. BIBER "King of spices"
" Black gold“
Na kraju se ostatak Evrope umorio od plaćanja visokih cena Veneciji za uvoz bibera i
odlučio je da preuzme stvari u svoje ruke.
Tako je započelo doba Kristofera Kolumba, Vaska de Game, Ser Fransisa Drejka i
drugih istraživača. I zaista, Kolumbo je napuno svoje brodove sa onim što je verovao
da je biber i doneo začin čak iz daleke Zapadne Indije. Tek u Španiji je otkrio da
njegovi brodovi nisu puni neprocenjivog bibera, već beskorisne čili paprike.

7. BIBER
Piper nigrum and its bioactive phyto-compounds is were also found to possess
important pharmacological properties.
Antimicrobial activity
Antioxidant effects against a series of reactive oxygen and nitrogen species
including the scavenging of superoxide anion, hydrogen peroxide, nitric oxide,
DPPH, ABTS
Anticancer effect against a number of cell lines from breast, colon, cervical, and
prostate through different mechanisms including cytotoxicity, apoptosis,
autophagy, and interference with signaling pathways.
antidiabetic property
hypolipidemic activity
Anti-inflammatory, analgesic, anticonvulsant, and neuroprotective effects

8. BIBER
The major bioactive compound identified in P. nigrum is piperine
(1-peperoyl piperidine)
piperic acid

9. BIBER
piperlonguminine
pellitorine
piperolein B

10. BIBER
piperamide

11. BIBER
piperettine
and (-)-kusunokinin, which also showed biological potency.

12. BIBER

13. BIBER
piperine (1-peperoyl piperidine)
Piperine exhibits diverse pharmacological activities like
antihypertensive and anti-platelets , antioxidant, antitumor,
antipyretic, analgesic, anti-inflammatory, antidiarrheal,
antispasmodic, hepato-protective, antibacterial, antifungal,
anti-thyroids, anti-apoptotic, anti-spermatogenic,
insecticidal and larvicidal activities etc.
piperine, which is present in the fruits in amounts of 1.7-7.4%.

14. BIBER
piperine (1-peperoyl piperidine)
piperine, which is present in the fruits in amounts of 1.7-7.4%.

15. BIBER
sastav

16. BIBER
sastav

17. BIBER
EO

18. BIBER
Piperine, a pungent alkaloid found in pepper, helps increase the
absorption of selenium, B-group vitamins, and beta-carotene, among
other nutrients.
Piperine also increases the bioavailability of certain compounds. This is
especially true when it comes to curcumin, the active compound of turmeric
that helps fight inflammation.
Piperine also interferes with inflammatory signaling mechanisms and
inhibits pro-inflammatory cytokines

19. BIBER
Piperine, an alkaloid present in pepper, could bind to novel coronavirus pro
teins and stop it from entering human cells, says IIT (ISM) study
Black pepper may hold the key for Corona fighting drug: Study
https://www.downtoearth.org.in/news/science-technology/black-pepper-may-
hold-the-key-for-corona-fighting-drug-study-73822

20. BIBER
Rout, Janmejaya et al. “In silico investigation of spice molecules as potent
inhibitor of SARS-CoV-2.”
Journal of biomolecular structure & dynamics, 1-15. 17 Sep. 2020, doi:10.1080/07391102.2020.1819879
The spice molecules that are used in our food have antiviral, antifungal and antimicrobial
properties. As spice molecules are consumed in the diet, hence its antiviral properties ag
ainst SARS-CoV-2 will benefit in a significant manner. Therefore,
in this work, the molecular docking of 30 selected spice molecules (screened through A
DME property) was performed to identify the potential inhibitors for the RBD Spro and M
pro of SARS-CoV-
2 We have found that though all the molecules bind actively with the SARS-CoV-2
RBD Spro and Mpro,
but Piperine has the highest binding affinity among the 30 screened molecules. Bes
ides, the comparative study between Piperine and currently used drugs show that Piperin
e is more effective.
https://www.researchgate.net/publication/344302854_In_silico_investigation_of_spice_molecules_as
_potent_inhibitor_of_SARS-CoV-2
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544943/

21. BIBER
Piperine possesses a strong anti-inflammatory function and therefore can be repurposed for
suppression of hyper inflammation induced during COVID-19. It downregulates PGEs
by inhibiting the expression levels of IL-6 and matrix metalloproteinases (MMP-13).
Piperine promotes innate immunity by promoting the phagocytic activity of phagocytes
and is known to inhibit LPS-induced expression of IRF-1 and
IRF-7 mRNA, phosphorylation of IRF-3, type 1IFN mRNA, and down-regulation of STAT-
1 activity. Few studies conducted on microglial cells have shown that piperine inhibits LPS-
Induced TNF-α, IL-6, IL-1β, and PGE2 production in
BV2 cells. Also, it found to inhibit the production of IL-2, and IFN-γ in
human peripheral blood mononuclear cells (PBMCs) .
Furthermore, piperine treatment found to reduce the production of
pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α, COX-2, nitric oxide synthase-
2, and NF-κB in the cerebral ischemia-reperfusion-induced inflammation rat
model. These findings indicate the strong anti-inflammatory activity of the piperine.

22. BIBER
Further, piperine is a potent antioxidant and protects against oxidative damage by neutralizing
free radicals, ROS, and hydroxyl radicals.
These results indicate that piperine possesses a direct antioxidant effect against various
free radicals . Because of these properties, piperine can be tried as a prophylactic or
therapeutic compound to protect from the oxidative stress and hyper inflammation
induced during the COVID-19.
Immune-Boosting, Antioxidant and Anti-
inflammatory Food Supplements Targeting Pathogenesis of COVID-19
https://www.frontiersin.org/articles/10.3389/fimmu.2020.570122/full

23. BIBER
Natural compounds as potential inhibitors of novel coronavirus (COVID-19)
main protease: An in silico study
https://www.researchsquare.com/article/rs-22839/v1

24. BIBER
Theoretical Molecular Docking Study of the Structural Disruption of the Viral 3CL-
Protease of COVID19 Induced by Binding of Capsaicin, Piperine and Curcumin
Part 1: A Comparative Study with Chloroquine and Hydrochloroquine Two
Antimalaric Drug
Preliminary results suggested that piperine, capsaicin, and curcumin have
the best docking scores and that they are capable of promoting structural
changes in the viral protease by inducing folding of the enzyme.
https://www.researchgate.net/publication/340466043_Theoretical_Molecular_Docki
ng_Study_of_the_Structural_Disruption_of_the_Viral_3CL-
Protease_of_COVID19_Induced_by_Binding_of_Capsaicin_Piperine_and_Curcumi
n_Part_1_A_Comparative_Study_with_Chloroquine

25. BIBER
Computational studies reveal piperine, the predominant oleoresin of
black pepper (Piper nigrum) as a potential inhibitor of SARS-CoV-2
(COVID-19)
This study suggests that consumption of black pepper may also help to
combat SARS-CoV-2 directly through possible antiviral effects, besides
its immunomodulatory functions.
https://www.researchgate.net/publication/344808285_Computational_studies_reveal
_piperine_the_predominant_oleoresin_of_black_pepper_Piper_nigrum_as_a_potent
ial_inhibitor_of_SARS-CoV-2_COVID-19

26. BIBER
Structure-based drug designing for potential antiviral activity of selected natural
products from Ayurveda against SARS-CoV-2 spike glycoprotein and its cellular
receptor
Our study exhibited that curcumin, nimbin, withaferin A, piperine, mangiferin, thebaine, berberine,
and andrographolide have significant binding affinity towards spike glycoprotein of SARS-CoV-2
and ACE2 receptor and may be useful as a therapeutic and/or prophylactic agent for restricting
viral attachment to the host cells.
However, few other natural products like resveratrol, quercetin, luteolin, naringenin,zingiberene,
and gallic acid has the significant binding affinity towards ACE2 receptor only and therefore may
be used for ACE2-mediated attachment inhibition of SARSCoV-2.
https://link.springer.com/article/10.1007/s13337-020-00598-8

27. BIBER